Abstract
BackgroundPrevious epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk.MethodsEligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score.ResultsEighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR).ConclusionsOur meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings.
Highlights
Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility
The results of our meta-analysis revealed that individuals with variant genotype (TT) were less susceptible to sepsis than individuals with CC or CT genotypes in overall comparison and Caucasian population, which was inconsistent with higher IL-1β levels associated with increased risk of sepsis
IL-1β plays an important role in sepsis and IL-1β is frequently over-expressed in sepsis, our meta-analysis indicated no significant association between the IL-1B-511 and −31 polymorphisms and sepsis risk, suggesting that IL-1β expression might influence sepsis progression via mechanisms other than regulation by the two promoter polymorphisms
Summary
Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. Sepsis is a complex clinical syndrome that results from a systemic inflammatory response to bacteria and/or bacterial products [1]. Though there have been many advances in the development of antibiotics and supportive care, sepsis remains a serious and deadly problem with high mortality rates worldwide [2]. Excessive IL-1 production is directly linked to the development of shock, multi-organ system failure, and death in patients and animals with sepsis, systemic inflammatory response syndrome, and septic shock [7]. Clinical trials with recombinant IL-1ra in the treatment of sepsis showed the highest mortality rate in those patients treated with the largest dose of IL-1ra, suggesting that overproduction of either pro-inflammatory mediators (IL-1α and IL-1β) or anti-inflammatory cytokines (IL-1ra) might lead to organ dysfunction and even death [8]
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