Prognostic Value of Interlukine-1 Receptor Antagonist and Tumor Necrosis Factor Gene Polymorphism in Systemic Inflammatory Response Syndrome

Objective: The aim of this work was to evaluate the prognostic value of TNF-a, IL-1ß, and IL-1ra genetic poly-morphism in SIRS patients. Patients: In this work 120 patients with SIRS admitted to ICU were included, as well 30 age, sex, weight, and body mass index matched healthy control subjects. Patients were divided into two groups of 60 patients each, a group with sepsis and a group with non sepsis. Methods: Clinical parameters, routine laboratory investi-gations, and a prognostic scoring system (APACHE II) were studied. Serum levels of TNF-a, IL-1ß, and IL-1ra as well as their corresponding genetic polymorphism were also examined. The relation between the cytokine serum levels, their different alleles and parameters of disease outcome were studied. Results: All studied cytokines were significant higher in non survivors more than survivors in total SIRS patients while in sepsis group TNF-a, and IL-1ra were significant higher in non survivors than survivors. In non sepsis group on the other hand IL-1ra was not significant different between survivors and non survivors while the other two cytokines were signif-icant higher in non survivors. There was statistical significant positive linear correlation between serum levels of TNF- a, IL-1ß, and IL-1ra cytokines on one hand and APACHE II scoring and mortality on the other hand in total SIRS patients and sepsis group. A ratio of pro/anti inflammatory cytokine (TNF-a x IL-1ß/ IL-1ra) was significantly higher in non survivors than survivors in total and non sepsis group while in sepsis group no significant difference in this ratio between survivors and non survivors. TNF-a serum levels was signif-icant higher in patients possessing allele 2 while no significant relation between other cytokine serum levels and their corre-sponding genetic polymorphism. There was no difference in frequency of distribution between control, sepsis group, and non sepsis group. TNF-a allele 2 was significant associated with non survivors in total SIRS patients and sepsis group while this relation not statistical significant in non sepsis. There was no significant association between non survivors and different IL-1ß alleles. IL-1ra allele A2 on the other hand associated with mortality in sepsis group only, but not in total SIRS patients or non sepsis group. Conclusion: The present results demonstrate that higher serum cytokine levels is related to mortality and a balance towards the anti-inflammatory response might be potentially protective in non septic patients but not in septic condition. TNF-a allele 2 polymorphism is associated with higher levels of TNF-a cytokine and poor outcome. In addition, Both TNF-a allele 2 and IL-1ra allele A2 were associated with poor outcome in septic but not in non septic patients, both TNF-a allele 2 and IL-1ra allele A2 may be viewed as predictor of poor outcome in sepsis.