Routinely used biomarkers of bacterial etiology of infection, such as C-reactive protein and procalcitonin, have limited usefulness for evaluation of infections since their expression is enhanced by a number of different conditions. Therefore, several inflammatory cytokines and chemokines were analyzed with sera from patients hospitalized for moderate bacterial and viral infectious diseases. In total, 57 subjects were enrolled: 21 patients with community-acquired bacterial infections, 26 patients with viral infections, and 10 healthy subjects (control cohorts). The laboratory analyses were performed using Luminex technology, and the following molecules were examined: IL-1Ra, IL-2, IL-4, IL-6, IL-8, TNF- α , INF- γ , MIP-1 β , and MCP-1. Bacterial etiology of infection was associated with significantly (P < 0.001) elevated serum concentrations of IL-1Ra, IL-2, IL-6, and TNF- α in comparison to levels observed in the sera of patients with viral infections. In the patients with bacterial infections, IL-1Ra and IL-8 demonstrated positive correlation with C-reactive protein, whereas, IL-1Ra, TNF- α , and MCP-1 correlated with procalcitonin. Furthermore, elevated levels of IL-1Ra, IL-6, and TNF- α decreased within 3 days of antibiotic therapy to levels observed in control subjects. The results show IL-1Ra as a potential useful biomarker of community-acquired bacterial infection.

Department of Infectious and Tropical Diseases 1st Faculty of Medicine Charles University Prague and Na Bulovce Hospital Prague Czech Republic

Zobrazit více v PubMed

Linares LF, Gomez-Reino JJ, Carreira PE. C-reactive protein (CRP) levels in systemic lupus erythematosus (SLE) Clinical Rheumatology. 1986;5(1):66–69. PubMed

Kanbayashi Y, Mukoyama N, Nishida K, et al. Two cases of malignant lymphoma with high fever and C-reactive protein (CRP) elevation after treatment with granulocyte colony-stimulating factor (G-CSF) Cancer & Chemotherapy. 2006;33(1):73–77. PubMed

Gonzalez MA, Selwyn AP. Endothelial function, inflammation, and prognosis in cardiovascular disease. American Journal of Medicine. 2003;115(8, supplement):99–106. PubMed

Amin DN, Pruitt JC, Schuetz P. Influence of major cardiopulmonary surgery on serum levels of procalcitonin and other inflammatory markers. Anaesthesia and Intensive Care. 2012;40(5):760–766. PubMed

Nylén ES, Al Arifi A, Becker KL, Snider RH, Jr., Alzeer A. Effect of classic heatstroke on serum procalcitonin. Critical Care Medicine. 1997;25(8):1362–1365. PubMed

Lisboa T, Seligman R, Diaz E, Rodriguez A, Teixeira PJZ, Rello J. C-reactive protein correlates with bacterial load and appropriate antibiotic therapy in suspected ventilator-associated pneumonia. Critical Care Medicine. 2008;36(1):166–171. PubMed

Charles PE, Tinel C, Barbar S, et al. Procalcitonin kinetics within the first days of sepsis: relationship with the appropriateness of antibiotic therapy and the outcome. Critical Care. 2009;13(2, article R38) PubMed PMC

De Pablo R, Monserrat J, Reyes E, et al. Mortality in patients with septic shock correlates with anti-inflammatory but not proinflammatory immunomodulatory molecules. Journal of Intensive Care Medicine. 2011;26(2):125–132. PubMed

Olszyna DP, Prins JM, Buis B, Van Deventer SJH, Speelman P, Van Der Poll T. Levels of inhibitors of tumor necrosis factor alpha and interleukin 1β in urine and sera of patients with urosepsis. Infection and Immunity. 1998;66(8):3527–3534. PubMed PMC

Sekiyama KD, Yoshiba M, Thomson AW. Circulating proinflammatory cytokines (IL-1β, TNF-α, and IL-6) and IL-1 receptor antagonist (IL-1Ra) in fulminant hepatic failure and acute hepatitis. Clinical and Experimental Immunology. 1994;98(1):71–77. PubMed PMC

de-Oliveira-Pinto LM, Gandini M, Freitas LP, et al. Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1β and CCL2/MCP-1 in dengue fever and parvovirosis. Memórias do Instituto Oswaldo Cruz. 2012;107(1):48–56. PubMed

Engel A, Kern P, Kern WV. Levels of cytokines and cytokine inhibitors in the neutropenic patient with α-hemolytic streptococcus shock syndrome. Clinical Infectious Diseases. 1996;23(4):785–789. PubMed

Urbonas V, Eidukaitė A, Tamulienė I. The diagnostic value of interleukin-6 and interleukin-8 for early prediction of bacteremia and sepsis in children with febrile neutropenia and cancer. Journal of Pediatric Hematology/Oncology. 2012;34(2):122–127. PubMed

McDade TW, Tallman PS, Adair LS, Borja J, Kuzawa CW. Comparative into the regulation of inflammation: levels and predictors of interleukin-6 and interleukin-10 in young adults in the Philippines. American Journal of Physical Antropology. 2011;146(3):373–384. PubMed PMC

Yudkin JS, Stehouwer CDA, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19(4):972–978. PubMed

Esposito K, Nappo F, Marfella R, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106(16):2067–2072. PubMed

Kolsuz M, Erginel S, Alataş O, et al. Acute phase reactants and cytokine levels in unilateral community-acquired pneumonia. Respiration. 2003;70(6):615–622. PubMed

Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Critical Care. 2010;14(1, article R15) PubMed PMC

Chalupa P, Beran O, Herwald H, Kaspříková N, Holub M. Evaluation of potential biomarkers for the discrimination of bacterial and viral infections. Infection. 2011;39(5):411–417. PubMed

Endeman H, Meijvis SCA, Rijkers GT, et al. Systemic cytokine response in patients with community-acquired pneumonia. European Respiratory Journal. 2011;37(6):1431–1438. PubMed

Beran O, Lawrence DA, Andersen N, et al. Sequential analysis of biomarkers in cerebrospinal fluid and serum during invasive meningococcal disease. European Journal of Clinical Microbiology and Infectious Diseases. 2009;28(7):793–799. PubMed PMC

Horcajada JP, Velasco M, Filella X, et al. Evaluation of inflammatory and renal-injury markers in women treated with antibiotics for acute pyelonephritis caused by Escherichia coli . Clinical and Diagnostic Laboratory Immunology. 2004;11(1):142–146. PubMed PMC

Martínez R, Menéndez R, Reyes S, et al. Factors associated with inflammatory cytokine patterns in community-acquired pneumonia. European Respiratory Journal. 2011;37(2):393–399. PubMed

Munford RS, Pugin J. Normal responses to injury prevent systemic inflammation and can be immunosuppressive. American Journal of Respiratory and Critical Care Medicine. 2001;163(2):316–321. PubMed

Blackwell TS, Christman JW. Sepsis and cytokines: current status. British Journal of Anaesthesia. 1996;77(1):110–117. PubMed

Mera S, Tatulescu D, Cismaru C, et al. Multiplex cytokine profiling in patients with sepsis. Acta Pathologica, Microbiologica, et Immunologica Scandinavica. 2011;119(2):155–163. PubMed

de Jager CPC, van Wijk PTL, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Critical Care. 2010;14(5, article R192) PubMed PMC

Paris MM, Friedland IR, Ehrett S, et al. Effect of interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor in animal models of infection. Journal of Infectious Diseases. 1995;171(1):161–169. PubMed

Christian LM, Iams JD, Porter K, Glaser R. Inflammatory responses to trivalent influenza virus vaccine among pregnant women. Vaccine. 2011;29(48):8982–8987. PubMed PMC

Bloos F, Hinder F, Becker K, et al. A multicenter trial to compare blood culture with polymerase chain reaction in severe human sepsis. Intensive Care Medicine. 2010;36(2):241–247. PubMed

Selected Biomarkers Correlate with the Origin and Severity of Sepsis