Objective To analyze the levels of circulating and cell-associated forms of interleukin-1 receptor antagonist (IL-1ra) and the spontaneous and the lipopolysaccharide- or streptococcus - induced ex vivo production of IL-1ra by isolated neutrophils. Design Cohort study. Setting A collaborative study between an intensive care unit and a research laboratory. Patients Septic patients (those with infectious systemic inflammatory response syndrome [SIRS]) and patients undergoing cardiac surgery with cardiopulmonary bypass (noninfectious SIRS). Measurements and Main Results Both noninfectious and infectious SIRS patients had enhanced levels of plasma IL-1ra. In septic patients, the increased level of IL-1ra associated with circulating leukocytes reflected the higher number of circulating neutrophils, because these cells, as well as peripheral blood mononuclear cells, contained similar levels of cell-associated forms of IL-1ra than those found at homeostasis in healthy controls. The analysis of the in vitro production of IL-1ra by neutrophils showed a decreased capacity of these cells to release the secreted form of IL-1ra on activation in all patients when compared with that capacity in healthy controls. In contrast, the production of the intracellular forms of IL-1ra was not altered in septic patients, but it was diminished in post-cardiopulmonary bypass patients. Conclusions The capacity of releasing IL-1ra by activated neutrophils from infectious or noninfectious SIRS patients was diminished. In contrast, the accumulation of intracellular IL-1ra in septic patients was not modified when compared with that in healthy controls. These ex vivo data illustrate that a different gene regulation of the secreted and intracellular forms of IL-1ra occurs during a pathologic situation like sepsis.
