IL-8 and its polymorphisms are involved in multiple acute and chronic inflammatory processes including pathological changes to surrounding structures of the teeth called periodontal diseases or periodontitis. The aim of this manuscript was to systematically review studies from 2006 to 2021 on IL-8 polymorphisms and their association with periodontitis. Literature analysis was done following the PRISMA protocol guidance using articles not older than 15 years (2006-2021). The search was carried out using PubMed (MEDLINE), ScienceDirect and Wiley Online Library databases. For the focus question, the PICO (population (P), intervention (I), control (C), and outcome (O)) study design protocol was used, and the following question was formulated: are IL-8 gene polymorphisms associated with periodontitis? A total of 2422 articles were found at the beginning of the search. After applying the inclusion and exclusion criteria, screening, and full-text article exclusion with reasons, 31 studies were included in the analysis. In conclusion, IL-8 and its gene polymorphisms are associated with an increased risk of periodontal diseases.

• Keywords
• IL-8, PRISMA protocol guidance, gene polymorphisms, literature review, periodontitis, serum level,
• MeSH
• Chronic Periodontitis * MeSH
• Interleukin-8 genetics   MeSH
• Humans MeSH
• Periodontitis * genetics   MeSH
• Polymorphism, Genetic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Interleukin-8 MeSH

Host genetic predispositions to dysregulated immune response can influence the development of the aggressive form of periodontitis (AgP) through susceptibility to oral dysbiosis and subsequent host-microbe interaction. This case-control study aimed to perform a multilocus analysis of functional variants in selected interleukin (IL) genes in patients with the generalized form of AgP in a homogenous population. Twelve polymorphisms in IL-1 gene cluster, IL-6 and its receptor, IL-10, IL-17A, and IL-18 were determined in 91 AgP patients and 210 controls. Analysis of seven selected periodontal bacteria in subgingival sulci/pockets was performed with a commercial DNA-microarray kit in a subgroup of 76 individuals. The pilot in vitro study included stimulation of peripheral blood monocytes (PBMC) from 20 individuals with periodontal bacteria and measurement of IL-10 levels using the Luminex method. Only the unctional polymorphism IL‑10-1087 A/G (rs1800896) and specific IL-10 haplotypes were associated with the development of the disease (P < 0.05, Pcorr > 0.05). Four bacterial species occurred more frequently in AgP than in controls (P < 0.01, Pcorr < 0.05). Elevated IL-10 levels were found in AgP patients, carriers of IL‑10-1087GG genotype, and PBMCs stimulated by periodontal bacteria (P < 0.05, Pcorr > 0.05). We therefore conclude that a combination of genetic predisposition to the altered expression of IL-10 and the presence of specific periodontal bacteria may contribute to Th1/Th2 balance disruption and AgP development.

• Keywords
• aggressive periodontitis, genetic predisposition, inflammation, interleukin, oral bacteria, polymorphism,
• MeSH
• Aggressive Periodontitis genetics   immunology   microbiology   MeSH
• Alleles MeSH
• Bacteria genetics   MeSH
• Adult MeSH
• Gene Frequency genetics   MeSH
• Genetic Predisposition to Disease genetics   MeSH
• Genotype MeSH
• Haplotypes genetics   MeSH
• Interleukin-1 genetics   MeSH
• Interleukin-10 genetics   MeSH
• Interleukin-17 genetics   MeSH
• Interleukin-18 genetics   MeSH
• Interleukin-6 genetics   MeSH
• Interleukins genetics   metabolism   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Humans MeSH
• Periodontitis genetics   immunology   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Interleukin-1 MeSH
• Interleukin-10 MeSH
• Interleukin-17 MeSH
• Interleukin-18 MeSH
• Interleukin-6 MeSH
• Interleukins MeSH

Periodontitis, an inflammatory disease caused by subgingival Gram-negative (G-) bacteria, is linked with loss of the connective tissue and destruction of the alveolar bone. In the regulation of inflammatory response, chemokine receptor 2 (CXCR2), a specific receptor for interleukin-8 and neutrophil chemoattractant, plays an important role. The first aim of this study was to investigate the CXCR2 gene variability in chronic periodontitis (CP) patients and healthy nonperiodontitis controls in the Czech population. The second aim was to find a relation between CXCR2 gene variants and the presence of periodontal bacteria. A total of 500 unrelated subjects participated in this case-control study. 329 CP patients and 171 healthy nonperiodontitis controls were analyzed using polymerase chain reaction techniques for three single-nucleotide polymorphisms (SNPs): +785C/T (rs2230054), +1208T/C (rs1126579), and +1440A/G (rs1126580). A DNA microarray detection kit was used for the investigation of the subgingival bacterial colonization, in a subgroup of CP subjects (N = 162). No significant differences in allele, genotype, haplotype, or haplogenotype frequencies of CXCR2 gene variants between patients with CP and healthy controls (P > 0.05) were determined. Nevertheless, Aggregatibacter actinomycetemcomitans was detected more frequently in men positive for the C allele of the CXCR2 +785C/T polymorphism (61.8% vs. 41.1%, P < 0.05; OR = 2.31, 95% CI = 1.03-5.20) and for the T allele of the CXCR2 +1208C/T variant (61.8% vs. 38.9%, P < 0.05; OR = 2.54, 95% CI = 1.13-5.71). In contrast, no statistically significant associations of CXCR2 variants with seven selected periodontal bacteria were found in women. Although none of the investigated SNPs in the CXCR2 gene was associated with CP, the CXCR2 gene variants can be associated with subgingival colonization of G- bacteria in men with CP in the Czech population.

• MeSH
• Aggregatibacter actinomycetemcomitans pathogenicity   MeSH
• Alleles MeSH
• Chronic Periodontitis genetics   microbiology   MeSH
• Adult MeSH
• Genotype MeSH
• Haplotypes genetics   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Receptors, Interleukin-8B genetics   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• CXCR2 protein, human MeSH Browser
• Receptors, Interleukin-8B MeSH

Recent studies have suggested a bidirectional relationship between chronic periodontitis (CP) and diabetes mellitus (DM). Immunoregulatory factors such as cytokines play an important role in etiopathogenesis of both diseases. The aim of this study was to analyze variability in interleukin-1 (IL-1) gene cluster and IL-1β plasma levels in patients with CP, DM, and a combination of both diseases. A total of 1016 individuals participating in this case-control study-225 healthy controls, 264 patients with CP, 132 with type 1 diabetes (T1DM), and 395 patients with type 2 diabetes (T2DM)-were genotyped using methods based on polymerase chain reaction for IL-1 gene polymorphisms (IL-1A (-889C/T, rs1800587), IL-1B (+3953C/T, rs1143634), and IL-1RN (gene for IL-1 receptor antagonist, IL-1RA, 86 bp tandem repeats in intron 2)). Levels of IL-1β were measured by Luminex methods in subgroups of controls, CP, T1DM + CP, and T2DM + CP subjects. Although no significant associations were found in the genotype and allele frequencies of IL-1A (-889C/T), significant differences in the allele frequencies of IL-1B (+3953C/T) were observed between controls and CP patients (P < 0.05). In T1DM patients, IL-1RN ∗ S "short" allele and IL-1RN 12 genotype were significantly less frequent than those in controls (P < 0.01). In haplotype analysis, TTL haplotype decreased the risk of CP development (P < 0.01), whereas CCS and CTL haplotypes (P < 0.01 and P < 0.05) were associated with T1DM. Although IL-1β levels were measured significantly higher in mononuclear cells after stimulation by mitogens, HSP70, or selected periodontal bacteria than in unstimulated cells, IL-1 genotypes did not correlate with circulating IL-1β levels. In the Czech population, significant associations between the IL-1B polymorphism with CP and the IL-1RN variant with T1DM were found. Haplotype analysis suggests that variability in IL-1 gene cluster may be one of the factors in the CP and T1DM pathogenesis, although single variants of these polymorphisms are not substantial for protein production.

• Publication type
• Journal Article MeSH

Chronic periodontitis (CP) and diabetes mellitus (DM) involve several aspects of immune functions, including neutrophil activity and cytokine biology. Considering the critical function of chemokine interleukin-8 (IL-8) in the inflammatory process, the aims of this study were to determine: (i) IL-8 plasma levels; (ii) IL-8 (-251A/T, rs4073) and its receptor 2 (CXCR2, +1208C/T, rs1126579) polymorphisms, and (iii) the presence of the selected periodontal bacteria in types 1 and 2 DM patients (T1DM and T2DM) and systemically healthy controls (HC) with known periodontal status. This case⁻control study comprises of 153 unrelated individuals: 36/44 patients suffering from T1DM+CP/T2DM+CP and 32/41 from HC+CP/non-periodontitis HC. Both the clinical and biochemical parameters were monitored. The genotypes were determined using qPCR, IL-8 plasma levels were measured using an ELISA kit. Subgingival bacterial colonization was analyzed with a DNA microarray detection kit. The IL-8 plasma levels differed significantly between non-periodontitis HC and T1DM+CP/T2DM+CP patients (P < 0.01). Even in HC+CP, IL-8 concentrations were significantly lower than in T1DM+CP/T2DM+CP patients (P ≤ 0.05). No significant associations between the IL-8 plasma levels and the studied IL-8 and CXCR2 polymorphisms or the occurrence of selected periodontal bacteria (P > 0.05) were found. CP does not influence the circulating IL-8 levels. Patients with T1DM+CP/T2DM+CP had higher circulating IL-8 levels than HC+CP/non-periodontitis HC.

• Keywords
• chemokines, chronic periodontitis, diabetes mellitus, interleukin-8, plasma, polymorphism,
• MeSH
• Biomarkers MeSH
• Chronic Periodontitis blood   genetics   microbiology   MeSH
• Diabetes Mellitus, Type 1 blood   genetics   MeSH
• Diabetes Mellitus, Type 2 blood   genetics   MeSH
• Adult MeSH
• Genetic Variation MeSH
• Interleukin-8 blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• CXCL8 protein, human MeSH Browser
• Interleukin-8 MeSH

Interleukin-17 contributes to the pathogenesis of type 1 diabetes mellitus (T1DM) and chronic periodontitis (CP). We analyzed IL-17A -197A/G and IL-17F +7488C/T polymorphisms in T1DM and CP and determined their associations with IL-17 production and occurrence of periopathogens. Totally 154 controls, 125 T1DM, and 244 CP patients were genotyped using 5' nuclease TaqMan(®) assays. Bacterial colonization was investigated by a DNA-microarray kit. Production of IL-17 after in vitro stimulation of mononuclear cells by mitogens and bacteria was examined by the Luminex system. Although no differences in the allele/genotype frequencies between patients with CP and T1DM + CP were found, the IL-17A -197 A allele increased the risk of T1DM (P < 0.05). Levels of HbA1c were significantly elevated in carriers of the A allele in T1DM patients (P < 0.05). Production of IL-17 by mononuclear cells of CP patients (unstimulated/stimulated by Porphyromonas gingivalis) was associated with IL-17A A allele (P < 0.05). IL-17A polymorphism increased the number of Tannerella forsythia and Treponema denticola in patients with CP and T1DM + CP, respectively (P < 0.05). IL-17A gene variability may influence control of T1DM and the "red complex" bacteria occurrence in patients with CP and T1DM + CP. Our findings demonstrated the functional relevance of the IL-17A polymorphism with higher IL-17 secretion in individuals with A allele.

• MeSH
• Alleles MeSH
• Chronic Periodontitis blood   genetics   microbiology   MeSH
• Diabetes Mellitus, Type 1 blood   genetics   MeSH
• Adult MeSH
• Gene Frequency genetics   MeSH
• Genotype MeSH
• Interleukin-17 blood   genetics   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Leukocytes, Mononuclear metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• IL17A protein, human MeSH Browser
• IL17F protein, human MeSH Browser
• Interleukin-17 MeSH