The Role Of IL-1 Family Gene Polymorphisms In Sepsis

The balance between pro-and anti-inflammatory cytokines is believed to be a central to the pathophysiology in sepsis. The cytokines of IL-1 family play a very important role in this process. In recent years, It has been indicated that genes encoding for IL-1 family cytokines are polymorphic and some of these alleles may correlate with the regulation of cytokine production. Although it was reported that the severity of chronic infectious and certain autoimmune diseases was influenced by polymorphisms of IL-1 family cytokines and some alleles contributed to the susceptibility to these diseases, the effects of IL-1 family gene polymorphisms on sepsis are still unknown.Objectives: 1. To test if IL-lA(intron 6, VNTR), IL-1B (-511,RFLP) and IL-1RN(intron 2,VNTR) polymorphisms are susceptibility to sepsis. 2. To determine the effects of those gene polymorphisms on the severity and outcome in sepsis. 3. To study their regulatory effects on cytokine production and pro-/anti-inflammatory cytokine ratios of PBMC in vitro.Methods: 60 cases of patients with sepsis as well as health individuals each were enrolled in this study. Subgroups were divided according to different allele, genotype and pro-/anti-inflammatory cytokine gene associations. Genome DNA was extracted from WBC for analysis of IL-1 family gene polymorphisms. APACHE II, MODS scores of patients were recorded. Half of both the patients and the health were selected randomly for analyzing the regulatory effects of the polymorphisms on cytokine production and pro-/anti-inflammatory cytokine ratios of PBMC in vitro. LPS (1ug/ml) stimulation was given followed by PBMC isolated and cultured for 24 hours . Total RNA was extracted 4 hours later. RT-PCR was performed for measuring the cytokine's mRNA expression. Cytokines concentration in plasma and supernatants was detected using ELISA kits.Results: It is failed to find the susceptibility of IL-1A and IL-1B alleles to sepsis except IL-RN allele2. However, the patients with the genotype of IL-1A 2.2,IL-1B 2.2 orIL-1RN 2.2 have higher APACHE II,MODS scores and mortality than the other genotypes. The APACHE IK MODS scores and mortality are significantly...