Increased plasma concentrations of interleukin-1 receptor antagonist in neonatal sepsis

Newborns are prone to severe infections and sepsis. Cytokines such as tumor necrosis factor-alpha and IL-1 beta play a major role in the initiation of the host response to infections. IL-1 receptor antagonist (IL-1ra) is a naturally occurring antagonist of IL-1 beta. We hypothesized that low IL-1ra plasma concentrations might contribute to the high morbidity and mortality of neonatal sepsis. We studied IL-1ra plasma concentrations during neonatal sepsis. Eleven newborns with severe infection or sepsis, 28 newborns suspected as having sepsis, and eight healthy newborns were enrolled in the study. IL-1ra plasma concentrations proved to be increased in the newborns with severe infections or sepsis (5635 +/- 411 ng/L) versus the concentrations in the suspected group (2597 +/- 433 ng/L) and the control group (273 +/- 88 ng/L) (p < 0.001). After the start of antibiotic therapy, the IL-1ra plasma concentrations remained high during the first 16 h. The IL-1 beta plasma concentrations were increased in the group with a proven infection (78 +/- 27 ng/L) versus the suspected group (37 +/- 7 ng/L) (p < 0.05). Interestingly, the mean Il-1RA plasma concentration is a factor 50-100 higher than the IL-1 beta plasma concentrations. We conclude that IL-1ra in newborns is produced in an amount equal to that in adults. An inadequate IL-1ra response does not seem to contribute to the increased morbidity and mortality of neonatal sepsis.