Interleukin-1 receptor antagonist production during infectious and noninfectious systemic inflammatory response syndrome.
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.


METHODS
Cohort study.


METHODS
A collaborative study between an intensive care unit and a research laboratory.


METHODS
Septic patients (those with infectious systemic inflammatory response syndrome [SIRS]) and patients undergoing cardiac surgery with cardiopulmonary bypass (noninfectious SIRS).


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-1 ra occurs during a pathologic situation like sepsis.
Marie
C
C
Unité d'Immuno-Allergie, Institut Pasteur, Paris.
Muret
J
J
Fitting
C
C
Payen
D
D
Cavaillon
J M
JM
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000097:blood*; D002315:Cardiopulmonary Bypass; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000097:blood; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000401:mortality
D018501:Antirheumatic Agents; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins