Heat stress (HS) in poultry husbandry is an important stressor and with increasing global temperatures its importance will increase. The negative effects of stress on the quality and quantity of poultry production are described in a range of research studies. However, a lack of attention is devoted to the impacts of HS on individual chicken immune cells and whole lymphoid tissue in birds. Oxidative stress and increased inflammation are accompanying processes of HS, but with deleterious effects on the whole organism. They play a key role in the inflammation and oxidative stress of the chicken immune system. There are a range of strategies that can help mitigate the adverse effects of HS in poultry. Phytochemicals are well studied and some of them report promising results to mitigate oxidative stress and inflammation, a major consequence of HS. Current studies revealed that mitigating these two main impacts of HS will be a key factor in solving the problem of increasing temperatures in poultry production. Improved function of the chicken immune system is another benefit of using phytochemicals in poultry due to the importance of poultry health management in today's post pandemic world. Based on the current literature, baicalin and baicalein have proven to have strong anti-inflammatory and antioxidative effects in mammalian and avian models. Taken together, this review is dedicated to collecting the literature about the known effects of HS on chicken immune cells and lymphoid tissue. The second part of the review is dedicated to the potential use of baicalin and baicalein in poultry to mitigate the negative impacts of HS on poultry production.

Laboratory of Animal Immunology and Biotechnology Department of Animal Morphology Physiology and Genetics Faculty of AgriSciences Mendel University in Brno 613 00 Brno Czech Republic

NPPC Research Institute for Animal Production in Nitra 951 41 Luzianky Slovakia

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Habibian M., Ghazi S., Moeini M.M., Abdolmohammadi A. Effects of dietary selenium and vitamin E on immune response and biological blood parameters of broilers reared under thermoneutral or heat stress conditions. Int. J. Biometeorol. 2014;58:741–752. doi: 10.1007/s00484-013-0654-y. PubMed DOI

Ebeid T.A., Suzuki T., Sugiyama T. High ambient temperature influences eggshell quality and calbindin-D28k localization of eggshell gland and all intestinal segments of laying hens. Poult. Sci. 2012;91:2282–2287. doi: 10.3382/ps.2011-01898. PubMed DOI

Nawab A., Ibtisham F., Li G., Kieser B., Wu J., Liu W., Zhao Y., Nawab Y., Li K., Xiao M., et al. Heat stress in poultry production: Mitigation strategies to overcome the future challenges facing the global poultry industry. J. Therm. Biol. 2018;78:131–139. doi: 10.1016/j.jtherbio.2018.08.010. PubMed DOI

Abdel-Moneim A.M.E., Shehata A.M., Khidr R.E., Paswan V.K., Ibrahim N.S., El-Ghoul A.A., Aldhumri S.A., Gabr S.A., Mesalam N.M., Elbaz A.M., et al. Nutritional manipulation to combat heat stress in poultry—A comprehensive review. J. Therm. Biol. 2021;98:102915. doi: 10.1016/j.jtherbio.2021.102915. PubMed DOI

Agunos A., Pierson F.W., Lungu B., Dunn P.A., Tablante N. Review of Nonfoodborne Zoonotic and Potentially Zoonotic Poultry Diseases. Avian Dis. 2016;60:553–575. doi: 10.1637/11413-032416-Review.1. PubMed DOI

Mashaly M.M., Hendricks G.L., 3rd, Kalama M.A., Gehad A.E., Abbas A.O., Patterson P.H. Effect of heat stress on production parameters and immune responses of commercial laying hens. Poult. Sci. 2004;83:889–894. doi: 10.1093/ps/83.6.889. PubMed DOI

Hirakawa R., Nurjanah S., Furukawa K., Murai A., Kikusato M., Nochi T., Toyomizu M. Heat Stress Causes Immune Abnormalities via Massive Damage to Effect Proliferation and Differentiation of Lymphocytes in Broiler Chickens. Front. Vet. Sci. 2020;7:46. doi: 10.3389/fvets.2020.00046. PubMed DOI PMC

Goel A., Ncho C.M., Choi Y.H. Regulation of gene expression in chickens by heat stress. J. Anim. Sci. Biotechnol. 2021;12:11. doi: 10.1186/s40104-020-00523-5. PubMed DOI PMC

Akbarian A., Michiels J., Degroote J., Majdeddin M., Golian A., De Smet S. Association between heat stress and oxidative stress in poultry; mitochondrial dysfunction and dietary interventions with phytochemicals. J. Anim. Sci. Biotechnol. 2016;28:37. doi: 10.1186/s40104-016-0097-5. PubMed DOI PMC

Mishra B., Jha R. Oxidative Stress in the Poultry Gut: Potential Challenges and Interventions. Front. Vet. Sci. 2019;4:60. doi: 10.3389/fvets.2019.00060. PubMed DOI PMC

Quinteiro-Filho W.M., Gomes A.V., Pinheiro M.L., Ribeiro A., Ferraz-de-Paula V., Astolfi-Ferreira C.S., Ferreira A.J., Palermo-Neto J. Heat stress impairs performance and induces intestinal inflammation in broiler chickens infected with Salmonella Enteritidis. Avian Pathol. 2012;41:421–427. doi: 10.1080/03079457.2012.709315. PubMed DOI

Lee M.T., Lin W.C., Lee T.T. Potential crosstalk of oxidative stress and immune response in poultry through phytochemicals—A review. Asian-Australas. J. Anim. Sci. 2019;32:309–319. doi: 10.5713/ajas.18.0538. PubMed DOI PMC

Liu L., Ren M., Ren K., Jin Y., Yan M. Heat stress impacts on broiler performance: A systematic review and meta-analysis. Poult. Sci. 2020;99:6205–6211. doi: 10.1016/j.psj.2020.08.019. PubMed DOI PMC

Mignon-Grasteau S., Moreri U., Narcy A., Rousseau X., Rodenburg T.B., Tixier-Boichard M., Zerjal T. Robustness to chronic heat stress in laying hens: A meta-analysis. Poult. Sci. 2015;94:586–600. doi: 10.3382/ps/pev028. PubMed DOI

Gonzalez-Esquerra R., Leeson S. Effects of acute versus chronic heat stress on broiler response to dietary protein. Poult Sci. 2005;84:1562–1569. doi: 10.1093/ps/84.10.1562. PubMed DOI

Liu L., Fu C., Yan M., Xie H., Li S., Yu Q., He S., He J. Resveratrol modulates intestinal morphology and HSP70/90, NF-κB and EGF expression in the jejunal mucosa of black-boned chickens on exposure to circular heat stress. Food Funct. 2016;7:1329–1338. doi: 10.1039/C5FO01338K. PubMed DOI

Habashy W.S., Milfort M.C., Fuller A.L., Attia Y.A., Rekaya R., Aggrey S.E. Effect of heat stress on protein utilization and nutrient transporters in meat-type chickens. Int. J. Biometeorol. 2017;61:2111–2118. doi: 10.1007/s00484-017-1414-1. PubMed DOI

Lin H., Zhang H.F., Du R., Gu X.H., Zhang Z.Y., Buyse J., Decuypere E. Thermoregulation responses of broiler chickens to humidity at different ambient temperatures. II. Four weeks of age. Poult. Sci. 2005;84:1173–1178. doi: 10.1093/ps/84.8.1173. PubMed DOI

Nawaz A.H., Amoah K., Leng Q.Y., Zheng J.H., Zhang W.L., Zhang L. Poultry Response to Heat Stress: Its Physiological, Metabolic, and Genetic Implications on Meat Production and Quality Including Strategies to Improve Broiler Production in a Warming World. Front. Vet. Sci. 2021;23:699081. doi: 10.3389/fvets.2021.699081. PubMed DOI PMC

Post J., Rebel J.M., ter Huurne A.A. Physiological effects of elevated plasma corticosterone concentrations in broiler chickens. An alternative means by which to assess the physiological effects of stress. Poult. Sci. 2003;82:1313–1318. doi: 10.1093/ps/82.8.1313. PubMed DOI

Lin H., Sui S.J., Jiao H.C., Buyse J., Decuypere E. Impaired development of broiler chickens by stress mimicked by corticosterone exposure. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2006;143:400–405. doi: 10.1016/j.cbpa.2005.12.030. PubMed DOI

Zaboli G., Huang X., Feng X., Ahn D.U. How can heat stress affect chicken meat quality?—A review. Poult. Sci. 2019;98:1551–1556. doi: 10.3382/ps/pey399. PubMed DOI

Bijur G.N., Jope R.S. Opposing actions of phosphatidylinositol 3-kinase and glycogen synthase kinase-3beta in the regulation of HSF-1 activity. J. Neurochem. 2000;75:2401–2408. doi: 10.1046/j.1471-4159.2000.0752401.x. PubMed DOI

Cedraz H., Gromboni J.G.G., Garcia A.A.P., Jr., Farias Filho R.V., Souza T.M., Oliveira E.R.D., Oliveira E.B.D., Nascimento C.S.D., Meneghetti C., Wenceslau A.A. Heat stress induces expression of HSP genes in genetically divergent chickens. PLoS ONE. 2017;12:e0186083. doi: 10.1371/journal.pone.0186083. PubMed DOI PMC

Ming J., Xie J., Xu P., Liu W., Ge X., Liu B., Hex Y., Cheng Y., Zhou Q., Pan L. Molecular cloning and expression of two HSP70 genes in the Wuchang bream (Megalobrama amblycephala Yih) Fish Shellfish Immunol. 2010;28:407–418. doi: 10.1016/j.fsi.2009.11.018. PubMed DOI

Maak S., Melesse A., Schmidt R., Schneider F., Von Lengerken G. Effect of long-term heat exposure on peripheral concentrations of heat shock protein 70 (Hsp70) and hormones in laying hens with different genotypes. Br. Poult. Sci. 2003;44:133–138. doi: 10.1080/0007166031000085319. PubMed DOI

Pockley A.G. Heat shock proteins as regulators of the immune response. Lancet. 2003;362:469–476. doi: 10.1016/S0140-6736(03)14075-5. PubMed DOI

Siddiqui S.H., Kang D., Park J., Khan M., Shim K. Chronic heat stress regulates the relation between heat shock protein and immunity in broiler small intestine. Sci. Rep. 2020;10:18872. doi: 10.1038/s41598-020-75885-x. PubMed DOI PMC

Zhen F.S., Du H.L., Xu H.P., Luo Q.B., Zhang X.Q. Tissue and allelic-specific expression of hsp70 gene in chickens: Basal and heat-stress-induced mRNA level quantified with real-time reverse transcriptase polymerase chain reaction. Br. Poult. Sci. 2006;47:449–455. doi: 10.1080/00071660600827690. PubMed DOI

Xie J., Tang L., Lu L., Zhang L., Xi L., Liu H.C., Odle J., Luo X. Differential expression of heat shock transcription factors and heat shock proteins after acute and chronic heat stress in laying chickens (Gallus gallus) PLoS ONE. 2014;9:e102204. doi: 10.1371/journal.pone.0102204. PubMed DOI PMC

Sun X., Zhang H., Sheikhahmadi A., Wang Y., Jiao H., Lin H., Song Z. Effects of heat stress on the gene expression of nutrient transporters in the jejunum of broiler chickens (Gallus gallus domesticus) Int. J. Biometeorol. 2015;59:127–135. doi: 10.1007/s00484-014-0829-1. PubMed DOI

Habashy W.S., Milfort M.C., Adomako K., Attia Y.A., Rekaya R., Aggrey S.E. Effect of heat stress on amino acid digestibility and transporters in meat-type chickens. Poult. Sci. 2017;96:2312–2319. doi: 10.3382/ps/pex027. PubMed DOI

Al-Zghoul M.B., Alliftawi A.R.S., Saleh K.M.M., Jaradat Z.W. Expression of digestive enzyme and intestinal transporter genes during chronic heat stress in the thermally manipulated broiler chicken. Poult. Sci. 2019;98:4113–4122. doi: 10.3382/ps/pez249. PubMed DOI

Ma B., Zhang L., Li J., Xing T., Jiang Y., Gao F. Heat stress alters muscle protein and amino acid metabolism and accelerates liver gluconeogenesis for energy supply in broilers. Poult. Sci. 2021;100:215–223. doi: 10.1016/j.psj.2020.09.090. PubMed DOI PMC

Zhu L., Liao R., Wu N., Zhu G., Yang C. Heat stress mediates changes in fecal microbiome and functional pathways of laying hens. Appl. Microbiol. Biotechnol. 2019;103:461–472. doi: 10.1007/s00253-018-9465-8. PubMed DOI

Shi D., Bai L., Qu Q., Zhou S., Yang M., Guo S., Li Q., Liu C. Impact of gut microbiota structure in heat-stressed broilers. Poult. Sci. 2019;98:2405–2413. doi: 10.3382/ps/pez026. PubMed DOI

Varmuzova K., Matulova M.E., Gerzova L., Cejkova D., Gardan-Salmon D., Panhéleux M., Robert F., Sisak F., Havlickova H., Rychlik I. Curcuma and Scutellaria plant extracts protect chickens against inflammation and Salmonella Enteritidis infection. Poult. Sci. 2015;94:2049–2058. doi: 10.3382/ps/pev190. PubMed DOI

Segain J.P., Raingeard de la Blétière D., Bourreille A., Leray V., Gervoisy N., Rosales C., Ferrier L., Bonnet C., Blottière H.M., Galmiche J.P. Butyrate inhibits inflammatory responses through NFkappaB inhibition: Implications for Crohn’s disease. Gut. 2000;47:397–403. doi: 10.1136/gut.47.3.397. PubMed DOI PMC

Cavaglieri C.R., Nishiyama A., Fernandes L.C., Curi R., Miles E.A., Calder P.C. Differential effects of short-chain fatty acids on proliferation and production of pro- and anti-inflammatory cytokines by cultured lymphocytes. Life Sci. 2003;73:1683–1690. doi: 10.1016/s0024-3205(03)00490-9. PubMed DOI

Donohoe D.R., Garge N., Zhang X., Sun W., O’Connell T.M., Bunger M.K., Bultman S.J. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011;13:517–526. doi: 10.1016/j.cmet.2011.02.018. PubMed DOI PMC

Sikandar A., Zaneb H., Younus M., Masood S., Aslam A., Khattak F., Ashraf S., Yousaf M.S., Rehman H. Effect of sodium butyrate on performance, immune status, microarchitecture of small intestinal mucosa and lymphoid organs in broiler chickens. Asian-Australas. J. Anim. Sci. 2017;30:690–699. doi: 10.5713/ajas.16.0824. PubMed DOI PMC

Zhao Y., Chen F., Wu W., Sun M., Bilotta A.J., Yao S., Xiao Y., Huang X., Eaves-Pyles T.D., Golovko G., et al. GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3. Mucosal. Immunol. 2018;11:752–762. doi: 10.1038/mi.2017.118. PubMed DOI PMC

Isobe J., Maeda S., Obata Y., Iizuka K., Nakamura Y., Fujimura Y., Kimizuka T., Hattori K., Kim Y.G., Morita T., et al. Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon. Int. Immunol. 2020;32:243–258. doi: 10.1093/intimm/dxz078. PubMed DOI

Alhenaky A., Abdelqader A., Abuajamieh M., Al-Fataftah A.R. The effect of heat stress on intestinal integrity and Salmonella invasion in broiler birds. J. Therm. Biol. 2017;70:9–14. doi: 10.1016/j.jtherbio.2017.10.015. PubMed DOI

Tabler T.W., Greene E.S., Orlowski S.K., Hiltz J.Z., Anthony N.B., Dridi S. Intestinal Barrier Integrity in Heat-Stressed Modern Broilers and Their Ancestor Wild Jungle Fowl. Front. Vet. Sci. 2020;7:249. doi: 10.3389/fvets.2020.00249. PubMed DOI PMC

Nanto-Hara F., Kikusato M., Ohwada S., Toyomizu M. Heat Stress Directly Affects Intestinal Integrity in Broiler Chickens. J. Poult. Sci. 2020;57:284–290. doi: 10.2141/jpsa.0190004. PubMed DOI PMC

Altan O., Pabuçcuoğlu A., Altan A., Konyalioğlu S., Bayraktar H. Effect of heat stress on oxidative stress, lipid peroxidation and some stress parameters in broilers. Br. Poult. Sci. 2003;44:545–550. doi: 10.1080/00071660310001618334. PubMed DOI

Pizzino G., Irrera N., Cucinotta M., Pallio G., Mannino F., Arcoraci V., Squadrito F., Altavilla D., Bitto A. Oxidative Stress: Harms and Benefits for Human Health. Oxid. Med. Cell. Longev. 2017;2017:8416763. doi: 10.1155/2017/8416763. PubMed DOI PMC

Yang L., Tan G.Y., Fu Y.Q., Feng J.H., Zhang M.H. Effects of acute heat stress and subsequent stress removal on function of hepatic mitochondrial respiration, ROS production and lipid peroxidation in broiler chickens. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 2010;151:204–208. doi: 10.1016/j.cbpc.2009.10.010. PubMed DOI

Huang C., Jiao H., Song Z., Zhao J., Wang X., Lin H. Heat stress impairs mitochondria functions and induces oxidative injury in broiler chickens. J. Anim. Sci. 2015;93:2144–2153. doi: 10.2527/jas.2014-8739. PubMed DOI

Del Vesco A.P., Gasparino E. Production of reactive oxygen species, gene expression, and enzymatic activity in quail subjected to acute heat stress. J. Anim. Sci. 2013;91:582–587. doi: 10.2527/jas.2012-5498. PubMed DOI

Mujahid A., Akiba Y., Toyomizu M. Acute heat stress induces oxidative stress and decreases adaptation in young white leghorn cockerels by downregulation of avian uncoupling protein. Poult. Sci. 2007;86:364–371. doi: 10.1093/ps/86.2.364. PubMed DOI

Surai P.F., Kochish I.I., Fisinin V.I., Kidd M.T. Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update. Antioxidants. 2019;8:235. doi: 10.3390/antiox8070235. PubMed DOI PMC

Del Vesco A.P., Khatlab A.S., Goes E.S.R., Utsunomiya K.S., Vieira J.S., Oliveira Neto A.R., Gasparino E. Age-related oxidative stress and antioxidant capacity in heat-stressed broilers. Animal. 2017;11:1783–1790. doi: 10.1017/S1751731117000386. PubMed DOI

Habashy W.S., Milfort M.C., Rekaya R., Aggrey S.E. Cellular antioxidant enzyme activity and biomarkers for oxidative stress are affected by heat stress. Int. J. Biometeorol. 2019;63:1569–1584. doi: 10.1007/s00484-019-01769-z. PubMed DOI

Attia Y.A., Al-Harthi M.A., El-Shafey A.S., Rehab Y.A., Kim W.K. Enhancing Tolerance of Broiler Chickens to Heat Stress by Supplementation with Vitamin E, Vitamin C and/or Probiotics. Ann. Anim. Sci. 2017;17:1155–1169. doi: 10.1515/aoas-2017-0012. DOI

Zhao F.Q., Zhang Z.W., Qu J.P., Yao H.D., Li M., Li S., Xu S.W. Cold stress induces antioxidants and Hsps in chicken immune organs. Cell Stress Chaperones. 2014;19:635–648. doi: 10.1007/s12192-013-0489-9. PubMed DOI PMC

Liu W.C., Zhu Y.R., Zhao Z.H., Jiang P., Yin F.Q. Effects of Dietary Supplementation of Algae-Derived Polysaccharides on Morphology, Tight Junctions, Antioxidant Capacity and Immune Response of Duodenum in Broilers under Heat Stress. Animals. 2021;11:2279. doi: 10.3390/ani11082279. PubMed DOI PMC

Ruff J., Barros T.L., Tellez G., Jr., Blankenship J., Lester H., Graham B.D., Selby C.A.M., Vuong C.N., Dridi S., Greene E.S., et al. Research Note: Evaluation of a heat stress model to induce gastrointestinal leakage in broiler chickens. Poult. Sci. 2020;99:1687–1692. doi: 10.1016/j.psj.2019.10.075. PubMed DOI PMC

Tang L.P., Li W.H., Liu Y.L., Lun J.C., He Y.M. Heat stress aggravates intestinal inflammation through TLR4-NF-κβ signaling pathway in Ma chickens infected with Escherichia coli O157:H7. Poult. Sci. 2021;100:101030. doi: 10.1016/j.psj.2021.101030. PubMed DOI PMC

Varasteh S., Braber S., Akbari P., Garssen J., Fink-Gremmels J. Differences in Susceptibility to Heat Stress along the Chicken Intestine and the Protective Effects of Galacto-Oligosaccharides. PLoS ONE. 2015;10:e0138975. doi: 10.1371/journal.pone.0138975. PubMed DOI PMC

He S., Yu Q., He Y., Hu R., Xia S., He J. Dietary resveratrol supplementation inhibits heat stress-induced high-activated innate immunity and inflammatory response in spleen of yellow-feather broilers. Poult. Sci. 2019;98:6378–6387. doi: 10.3382/ps/pez471. PubMed DOI PMC

Medzhitov R., Horng T. Transcriptional control of the inflammatory response. Nat. Rev. Immunol. 2009;9:692–703. doi: 10.1038/nri2634. PubMed DOI

Prince L.R., Allen L., Jones E.C., Hellewell P.G., Dower S.K., Whyte M.K., Sabroe I. The role of interleukin-1beta in direct and toll-like receptor 4-mediated neutrophil activation and survival. Am. J. Pathol. 2004;165:1819–1826. doi: 10.1016/S0002-9440(10)63437-2. PubMed DOI PMC

Lynagh G.R., Bailey M., Kaiser P. Interleukin-6 is produced during both murine and avian Eimeria infections. Vet. Immunol. Immunopathol. 2000;76:89–102. doi: 10.1016/s0165-2427(00)00203-8. PubMed DOI

Yu H., Zou W., Wang X., Dai G., Zhang T., Zhang G., Xie K., Wang J., Shi H. Research Note: Correlation analysis of interleukin-6, interleukin-8, and C-C motif chemokine ligand 2 gene expression in chicken spleen and cecal tissues after Eimeria tenella infection in vivo. Poult. Sci. 2020;99:1326–1331. doi: 10.1016/j.psj.2019.10.071. PubMed DOI PMC

Jang D.I., Lee A.H., Shin H.Y., Song H.R., Park J.H., Kang T.B., Lee S.R., Yang S.H. The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics. Int. J. Mol. Sci. 2021;22:2719. doi: 10.3390/ijms22052719. PubMed DOI PMC

Calcagni E., Elenkov I. Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. Ann. N. Y. Acad. Sci. 2006;1069:62–76. doi: 10.1196/annals.1351.006. PubMed DOI

Aengwanich W. Comparative ability to tolerate heat between thai indigenous chickens, thai indigenous chickens crossbred and broilers by using heterophil/lymphocyte ratio. Pak. J. Biol. Sci. 2007;10:1840–1844. doi: 10.3923/pjbs.2007.1840.1844. PubMed DOI

Pamok S., Aengwanich W., Komutrin T. Adaptation to oxidative stress and impact of chronic oxidative stress on immunity in heat-stressed broilers. J. Therm. Biol. 2009;34:353–357. doi: 10.1016/j.jtherbio.2009.06.003. DOI

Freeman G.J., Wherry E.J., Ahmed R., Sharpe A.H. Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade. J. Exp. Med. 2006;203:2223–2227. doi: 10.1084/jem.20061800. PubMed DOI PMC

Reddy V.R.A.P., Mwangi W., Sadigh Y., Nair V. In vitro Interactions of Chicken Programmed Cell Death 1 (PD-1) and PD-1 Ligand-1 (PD-L1) Front. Cell. Infect. Microbiol. 2019;19:436. doi: 10.3389/fcimb.2019.00436. PubMed DOI PMC

Chai S.J., Cole D., Nisler A., Mahon B.E. Poultry: The most common food in outbreaks with known pathogens, United States, 1998–2012. Epidemiol. Infect. 2017;145:316–325. doi: 10.1017/S0950268816002375. PubMed DOI PMC

Taylor E.V., Herman K.M., Ailes E.C., Fitzgerald C., Yoder J.S., Mahon B.E., Tauxe R.V. Common source outbreaks of Campylobacter infection in the USA, 1997-2008. Epidemiol. Infect. 2013;141:987–996. doi: 10.1017/S0950268812001744. PubMed DOI PMC

Beczkiewicz A.T.E., Kowalcyk B.B. Risk Factors for Salmonella Contamination of Whole Chicken Carcasses following Changes in U.S. Regulatory Oversight. J. Food Prot. 2021;84:1713–1721. doi: 10.4315/JFP-21-144. PubMed DOI

Jorgensen F., Ellis-Iversen J., Rushton S., Bull S.A., Harris S.A., Bryan S.J., Gonzalez A., Humphrey T.J. Influence of season and geography on Campylobacter jejuni and C. coli subtypes in housed broiler flocks reared in Great Britain. Appl. Environ. Microbiol. 2011;77:3741–3748. doi: 10.1128/AEM.02444-10. PubMed DOI PMC

Williams M.S., Golden N.J., Ebel E.D., Crarey E.T., Tate H.P. Temporal patterns of Campylobacter contamination on chicken and their relationship to campylobacteriosis cases in the United States. Int. J. Food Microbiol. 2015;208:114–121. doi: 10.1016/j.ijfoodmicro.2015.05.018. PubMed DOI

Song J., Xiao K., Ke Y.L., Jiao L.F., Hu C.H., Diao Q.Y., Shi B., Zou X.T. Effect of a probiotic mixture on intestinal microflora, morphology, and barrier integrity of broilers subjected to heat stress. Poult. Sci. 2014;93:581–588. doi: 10.3382/ps.2013-03455. PubMed DOI

Zaytsoff S.J.M., Uwiera R.R.E., Inglis G.D. Physiological Stress Mediated by Corticosterone Administration Alters Intestinal Bacterial Communities and Increases the Relative Abundance of Clostridium perfringens in the Small Intestine of Chickens. Microorganisms. 2020;8:1518. doi: 10.3390/microorganisms8101518. PubMed DOI PMC

Zaytsoff S.J.M., Lyons S.M., Garner A.M., Uwiera R.R.E., Zandberg W.F., Abbott D.W., Inglis G.D. Host responses to Clostridium perfringens challenge in a chicken model of chronic stress. Gut Pathog. 2020;12:24. doi: 10.1186/s13099-020-00362-9. PubMed DOI PMC

Ma S., Qiao X., Xu Y., Wang L., Zhou H., Jiang Y., Cui W., Huang X., Wang X., Tang L., et al. Screening and Identification of a Chicken Dendritic Cell Binding Peptide by Using a Phage Display Library. Front. Immunol. 2019;6:1853. doi: 10.3389/fimmu.2019.01853. PubMed DOI PMC

Van Goor A., Slawinska A., Schmidt C.J., Lamont S.J. Distinct functional responses to stressors of bone marrow derived dendritic cells from diverse inbred chicken lines. Dev. Comp. Immunol. 2016;63:96–110. doi: 10.1016/j.dci.2016.05.016. PubMed DOI

Mills C.D., Leyy K. M1 and M2 macrophages: The chicken and the egg of immunity. J. Innate Immun. 2014;6:716–726. doi: 10.1159/000364945. PubMed DOI PMC

Slawinska A., Hsieh J.C., Schmidt C.J., Lamont S.J. Heat Stress and Lipopolysaccharide Stimulation of Chicken Macrophage-Like Cell Line Activates Expression of Distinct Sets of Genes. PLoS ONE. 2016;11:e0164575. doi: 10.1371/journal.pone.0164575. PubMed DOI PMC

Quinteiro-Filho W.M., Ribeiro A., Ferraz-de-Paula V., Pinheiro M.L., Sakai M., Sá L.R., Ferreira A.J., Palermo-Neto J. Heat stress impairs performance parameters, induces intestinal injury, and decreases macrophage activity in broiler chickens. Poult. Sci. 2010;89:1905–1914. doi: 10.3382/ps.2010-00812. PubMed DOI

Vega V.L., Crotty Alexander L.E., Charles W., Hwangy J.H., Nizet V., De Maio A. Activation of the stress response in macrophages alters the M1/M2 balance by enhancing bacterial killing and IL-10 expression. J. Mol. Med. 2014;92:1305–1317. doi: 10.1007/s00109-014-1201-y. PubMed DOI

Zhang H., Majdeddin M., Gaublomme D., Taminiau B., Boone M., Elewaut D., Daube G., Josipovic I., Zhang K., Michiels J. 25-hydroxycholecalciferol reverses heat induced alterations in bone quality in finisher broilers associated with effects on intestinal integrity and inflammation. J. Anim. Sci. Biotechnol. 2021;12:104. doi: 10.1186/s40104-021-00627-6. PubMed DOI PMC

Honda B.T., Calefi A.S., Costola-de-Souza C., Quinteiro-Filho W.M., da Silva Fonseca J.G., de Paula V.F., Palermo-Neto J. Effects of heat stress on peripheral T and B lymphocyte profiles and IgG and IgM serum levels in broiler chickens vaccinated for Newcastle disease virus. Poult. Sci. 2015;94:2375–2381. doi: 10.3382/ps/pev192. PubMed DOI

Tang J., Chen Z. The protective effect of γ-aminobutyric acid on the development of immune function in chickens under heat stress. J. Anim. Physiol. Anim. Nutr. 2016;100:768–777. doi: 10.1111/jpn.12385. PubMed DOI

Wu Q., Liu Z., Jiao C., Cheng B., Li S., Ma Y., Wang Y., Wang Y. Effects of Glutamine on Lymphocyte Proliferation and Intestinal Mucosal Immune Response in Heat-stressed Broilers. Braz. J. Poult. Sci. 2021;23:eRBCA-2019-1207. doi: 10.1590/1806-9061-2019-1207. DOI

Chen Z., Zhou Y.-W., Liang C., Jiang Y.-Y., Xie L.-J. Effects of γ-aminobutyric acid on the tissue structure, antioxidant activity, cell apoptosis, and cytokine contents of bursa of Fabricius in chicks under heat stress. Arch. Anim. Breed. 2016;59:97–105. doi: 10.5194/aab-59-97-2016. DOI

Bartlett J.R., Smith M.O. Effects of different levels of zinc on the performance and immunocompetence of broilers under heat stress. Poult. Sci. 2003;82:1580–1588. doi: 10.1093/ps/82.10.1580. PubMed DOI

Jahanian R., Rasouli E. Dietary chromium methionine supplementation could alleviate immunosuppressive effects of heat stress in broiler chicks. J. Anim. Sci. 2015;93:3355–3363. doi: 10.2527/jas.2014-8807. PubMed DOI

Davidson N.J., Boyd R.L. Delineation of chicken thymocytes by CD3-TCR complex, CD4 and CD8 antigen expression reveals phylogenically conserved and novel thymocyte subsets. Int. Immunol. 1992;4:1175–1182. doi: 10.1093/intimm/4.10.1175. PubMed DOI

Trout J.M., Mashaly M.M. The effects of adrenocorticotropic hormone and heat stress on the distribution of lymphocyte populations in immature male chickens. Poult. Sci. 1994;73:1694–1698. doi: 10.3382/ps.0731694. PubMed DOI

Trout J.M., Mashaly M.M. Effects of in vitro corticosterone on chicken T- and B-lymphocyte proliferation. Br. Poult. Sci. 1995;36:813–820. doi: 10.1080/00071669508417826. PubMed DOI

Soleimani A.F., Zulkifli I., Omar A.R., Raha A.R. Physiological responses of 3 chicken breeds to acute heat stress. Poult. Sci. 2011;90:1435–1440. doi: 10.3382/ps.2011-01381. PubMed DOI

Lee C., Kim J.H., Kil D.Y. Comparison of stress biomarkers in laying hens raised under a long-term multiple stress condition. Poult. Sci. 2022;101:101868. doi: 10.1016/j.psj.2022.101868. PubMed DOI PMC

Al-Murrani W.K., Kassab A., Al-Sam H.Z., Al-Athari A.M.K. Heterophil/lymphocyte ratio as a selection criterion for heat resistance in domestic fowls. Br. Poult. Sci. 1997;38:159–163. doi: 10.1080/00071669708417962. PubMed DOI

Thiam M., Barreto Sánchez A.L., Zhang J., Wen J., Zhao G., Wang Q. Investigation of the Potential of Heterophil/Lymphocyte Ratio as a Biomarker to Predict Colonization Resistance and Inflammatory Response to Salmonella enteritidis Infection in Chicken. Pathogens. 2022;11:72. doi: 10.3390/pathogens11010072. PubMed DOI PMC

Wang J., Zhu B., Wen J., Li Q., Zhao G. Genome-Wide Association Study and Pathway Analysis for Heterophil/Lymphocyte (H/L) Ratio in Chicken. Genes. 2020;11:1005. doi: 10.3390/genes11091005. PubMed DOI PMC

Chen H., Xu Y., Wang J., Zhao W., Ruan H. Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat. Int. J. Clin. Exp. Pathol. 2015;8:10139–10147. PubMed PMC

Dinda B., Dinda S., DasSharma S., Banik R., Chakraborty A., Dinda M. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. Eur. J. Med. Chem. 2017;5:68–80. doi: 10.1016/j.ejmech.2017.03.004. PubMed DOI

Shieh D.E., Liu L.T., Lin C.C. Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Res. 2000;20:2861–2865. PubMed

Tu X.K., Yang W.Z., Shi S.S., Chen Y., Wang C.H., Chen C.M., Chen Z. Baicalin inhibits TLR2/4 signaling pathway in rat brain following permanent cerebral ischemia. Inflammation. 2011;34:463–470. doi: 10.1007/s10753-010-9254-8. PubMed DOI

Dong S.J., Zhong Y.Q., Lu W.T., Li G.H., Jiang H.L., Mao B. Baicalin Inhibits Lipopolysaccharide-Induced Inflammation Through Signaling NF-κβ Pathway in HBE16 Airway Epithelial Cells. Inflammation. 2015;38:1493–1501. doi: 10.1007/s10753-015-0124-2. PubMed DOI

Kim Y.J., Kim H.J., Lee J.Y., Kim D.H., Kang M.S., Park W. Anti-Inflammatory Effect of Baicalein on Polyinosinic–Polycytidylic Acid-Induced RAW 264.7 Mouse Macrophages. Viruses. 2018;10:224. doi: 10.3390/v10050224. PubMed DOI PMC

Ren M., Zhao Y., He Z., Lin J., Xu C., Liu F., Hu R., Deng H., Wang Y. Baicalein inhibits inflammatory response and promotes osteogenic activity in periodontal ligament cells challenged with lipopolysaccharides. BMC Complement. Med. Ther. 2021;21:43. doi: 10.1186/s12906-021-03213-5. PubMed DOI PMC

Lee W., Ku S.K., Bae J.S. Anti-inflammatory effects of Baicalin, Baicalein, and Wogonin in vitro and in vivo. Inflammation. 2015;38:110–125. doi: 10.1007/s10753-014-0013-0. PubMed DOI

Peng-Fei L., Fu-Gen H., Bin-Bin D., Tian-Sheng D., Xiang-Lin H., Ming-Qin Z. Purification and antioxidant activities of baicalin isolated from the root of huangqin (Scutellaria baicalensis gcorsi) J. Food Sci. Technol. 2013;50:615–619. doi: 10.1007/s13197-012-0857-y. PubMed DOI PMC

Woźniak D., Dryś A., Matkowski A. Antiradical and antioxidant activity of flavones from Scutellariae baicalensis radix. Nat. Prod. Res. 2015;29:1567–1570. doi: 10.1080/14786419.2014.983920. PubMed DOI

Perez C.A., Wei Y., Guo M. Iron-binding and anti-Fenton properties of baicalein and baicalin. J. Inorg. Biochem. 2009;103:326–332. doi: 10.1016/j.jinorgbio.2008.11.003. PubMed DOI PMC

de Oliveira M.R., Nabavi S.F., Habtemariam S., Erdogan Orhan I., Daglia M., Nabavi S.M. The effects of baicalein and baicalin on mitochondrial function and dynamics: A review. Pharmacol. Res. 2015;100:296–308. doi: 10.1016/j.phrs.2015.08.021. PubMed DOI

Lee H.J., Noh Y.H., Lee D.Y., Kim Y.S., Kim K.Y., Chung Y.H., Lee W.B., Kim S.S. Baicalein attenuates 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. Eur. J. Cell Biol. 2005;84:897–905. doi: 10.1016/j.ejcb.2005.07.003. PubMed DOI

Liu B., Jian Z., Li Q., Li K., Wang Z., Liu L., Tang L., Yi X., Wang H., Li C., et al. Baicalein protects human melanocytes from H2O2-induced apoptosis via inhibiting mitochondria-dependent caspase activation and the p38 MAPK pathway. Free Radic. Biol. Med. 2012;53:183–193. doi: 10.1016/j.freeradbiomed.2012.04.015. PubMed DOI

Lenoir M., Martín R., Torres-Maravilla E., Chadi S., González-Dávila P., Sokol H., Langella P., Chain F., Bermúdez-Humarán L.G. Butyrate mediates anti-inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through Dact3. Gut Microbes. 2020;12:1826748. doi: 10.1080/19490976.2020.1826748. PubMed DOI PMC

Króliczewska B., Graczyk S., Króliczewski J., Pliszczak-Król A., Miśta D., Zawadzki W. Investigation of the immune effects of Scutellaria baicalensis on blood leukocytes and selected organs of the chicken’s lymphatic system. J. Anim. Sci. Biotechnol. 2017;8:22. doi: 10.1186/s40104-017-0152-x. PubMed DOI PMC

Peng L.Y., Yuan M., Song K., Yu J.L., Li J.H., Huang J.N., Yi P.F., Fu B.D., Shen H.Q. Baicalin alleviated APEC-induced acute lung injury in chicken by inhibiting NF-κβ pathway activation. Int. Immunopharmacol. 2019;72:467–472. doi: 10.1016/j.intimp.2019.04.046. PubMed DOI

Cheng P., Wang T., Li W., Muhammad I., Wang H., Sunx X., Yang Y., Li J., Xiao T., Zhang X. Baicalin Alleviates Lipopolysaccharide-Induced Liver Inflammation in Chicken by Suppressing TLR4-Mediated NF-κβ Pathway. Front. Pharmacol. 2017;18:547. doi: 10.3389/fphar.2017.00547. PubMed DOI PMC

Zhang X., Zhao Q., Ci X., Chen S., Chen L., Lian J., Xie Z., Ye Y., Lv H., Li H., et al. Effect of Baicalin on Bacterial Secondary Infection and Inflammation Caused by H9N2 AIV Infection in Chickens. Biomed. Res. Int. 2020;18:2524314. doi: 10.1155/2020/2524314. PubMed DOI PMC

Zou M., Yang L., Niu L., Zhao Y., Sun Y., Fu Y., Pengy X. Baicalin ameliorates Mycoplasma gallisepticum-induced lung inflammation in chicken by inhibiting TLR6-mediated NF-κβ signalling. Br. Poult. Sci. 2021;62:199–210. doi: 10.1080/00071668.2020.1847251. PubMed DOI

Wang J., Ishfaq M., Li J. Baicalin ameliorates Mycoplasma gallisepticum-induced inflammatory injury in the chicken lung through regulating the intestinal microbiota and phenylalanine metabolism. Food Funct. 2021;12:4092–4104. doi: 10.1039/D1FO00055A. PubMed DOI

Ishfaq M., Zhang W., Hu W., Waqas Ali Shah S., Liu Y., Wang J., Wu Z., Ahmad I., Li J. Antagonistic Effects Of Baicalin On Mycoplasma gallisepticum-Induced Inflammation And Apoptosis By Restoring Energy Metabolism In The Chicken Lungs. Infect. Drug Resist. 2019;12:3075–3089. doi: 10.2147/IDR.S223085. PubMed DOI PMC

Ishfaq M., Zhang W., Liu Y., Wang J., Wu Z., Shah S.W., Li R., Miao Y., Chen C., Li J. Baicalin attenuated Mycoplasma gallisepticum-induced immune impairment in chicken bursa of fabricius through modulation of autophagy and inhibited inflammation and apoptosis. J. Sci. Food Agric. 2021;101:880–890. doi: 10.1002/jsfa.10695. PubMed DOI

Wu Z., Chen C., Miao Y., Liu Y., Zhang Q., Li R., Ding L., Ishfaq M., Li J. Baicalin Attenuates Mycoplasma gallisepticum-Induced Inflammation via Inhibition of the TLR2-NF-κβ Pathway in Chicken and DF-1 Cells. Infect. Drug Resist. 2019;20:3911–3923. doi: 10.2147/IDR.S231908. PubMed DOI PMC

Li J., Qiao Z., Hu W., Zhang W., Shah S.W.A., Ishfaq M. Baicalin mitigated Mycoplasma gallisepticum-induced structural damage and attenuated oxidative stress and apoptosis in chicken thymus through the Nrf2/HO-1 defence pathway. Vet. Res. 2019;50:83. doi: 10.1186/s13567-019-0703-6. PubMed DOI PMC

Ishfaq M., Chen C., Bao J., Zhang W., Wu Z., Wang J., Liu Y., Tian E., Hamid S., Li R., et al. Baicalin ameliorates oxidative stress and apoptosis by restoring mitochondrial dynamics in the spleen of chickens via the opposite modulation of NF-κβ and Nrf2/HO-1 signaling pathway during Mycoplasma gallisepticum infection. Poult. Sci. 2019;98:6296–6310. doi: 10.3382/ps/pez406. PubMed DOI PMC

Cheng X., Cao Z., Luo J., Hu R., Cao H., Guo X., Xing C., Yang F., Zhuang Y., Hu G. Baicalin ameliorates APEC-induced intestinal injury in chicks by inhibiting the PI3K/AKT-mediated NF-κβ signaling pathway. Poult. Sci. 2022;101:101572. doi: 10.1016/j.psj.2021.101572. PubMed DOI PMC

Xu J., Li S., Jiang L., Gao X., Liu W., Zhu X., Huang W., Zhao H., Wei Z., Wang K., et al. Baicalin protects against zearalenone-induced chicks liver and kidney injury by inhibiting expression of oxidative stress, inflammatory cytokines and caspase signaling pathway. Int. Immunopharmacol. 2021;100:108097. doi: 10.1016/j.intimp.2021.108097. PubMed DOI

Zhou Y., Mao S., Zhou M. Effect of the flavonoid baicalein as a feed additive on the growth performance, immunity, and antioxidant capacity of broiler chickens. Poult. Sci. 2019;98:2790–2799. doi: 10.3382/ps/pez071. PubMed DOI

Tu I.H., Yen H.T., Cheng H.W., Chiu J.H. Baicalein protects chicken embryonic cardiomyocyte against hypoxia-reoxygenation injury via mu- and delta- but not kappa-opioid receptor signaling. Eur. J. Pharmacol. 2008;588:251–258. doi: 10.1016/j.ejphar.2008.04.003. PubMed DOI

Li Y., Yang D., Jia Y., He L., Li J., Yu C., Liao C., Yu Z., Zhang C. Research Note: Anti-inflammatory effects and antiviral activities of baicalein and chlorogenic acid against infectious bursal disease virus in embryonic eggs. Poult. Sci. 2021;100:100987. doi: 10.1016/j.psj.2021.01.010. PubMed DOI PMC

Xiao Y., Halter B., Boyer C., Cline M.A., Liu D., Gilbert E.R. Dietary Supplementation of Baicalein Affects Gene Expression in Broiler Adipose Tissue During the First Week Post-hatch. Front. Physiol. 2021;25:697384. doi: 10.3389/fphys.2021.697384. PubMed DOI PMC