抄録
Objective: To evaluate the effect of genotypic differences and the blood interleukin-1 receptor antagonist (IL-1ra) / interleukin-1β (IL-1β) levels ratio within IL-1 gene cluster polymorphisms on the outcome. Methods: One hundred and ninety consecutive critically ill patients recruited on admission to the ICU, regardless of diagnosis, were studied. Interleukin-6 (IL-6) blood levels were measured daily with chemiluminescent enzyme immunoassay. IL-1β and IL-1ra blood levels at corresponding time when routinely measured IL-6 showed maximal values were measured retrospectively with enzyme amplified sensitivity immunoassay. Single nucleotide polymorphisms at position -511 and +3953 sites of the IL-1β (IL-1β-511*C/T and IL1β+3953*C/T) were identified with restriction fragment length polymorphism method. IL-1ra intron 2nd various number of tandem repeat polymorphism (IL-1RN*1-5) was identified after polymerase chain reaction with gel electrophoresis. Results: IL-1RN*1.1 homozygotes had significantly higher survival (P = 0.04) and higher blood IL-1ra/IL-1β ratio (P = 0.01) than the other genotypes in IL-1RN*1-5. However, all those three polymorphisms (IL-1β-511*C/T, IL-1β+3953*C/T, and IL-1RN*1-5) solely affect neither IL-1β nor IL-1ra blood levels in each. Conclusions: Non-IL-1RN*1 alleles are associated with poor outcome and decrease in IL-1ra/IL-1β ratio causing overproduction of IL-6. Therefore, IL-1ra/IL-1β imbalance is considered to have induced the cytokine network collapse in those genetically high risk patients for hypercytokinemia.
