THE PATTERN OF INTERLEUKIN-1-BETA (IL-1-BETA) AND ITS MODULATING AGENTS IL-1 RECEPTOR ANTAGONIST AND IL-1 SOLUBLE RECEPTOR-TYPE-II IN ACUTEMENINGOCOCCAL INFECTIONS

Interleukin-1 beta (IL-1 beta) is considered an important mediator in the pathogenesis of septic shock or bacterial meningitis. Its activity is specifically modulated by IL-1 receptor antagonist (IL-1Ra) and IL -1 soluble receptor type II (IL-1sRII). We now describe the time-cours e of IL-1 beta and these modulating agents in 59 patients with acute m eningococcal infections, the prototype human disease of acute endotoxi n exposure, Plasma IL-1 beta was increased only in severe shock and no rmalized within 12 to 24 hours, indicating that patients were admitted in an early stage of cytokine activation. Increased IL-1 beta values in cerebrospinal fluid (CSF) were confined to patients with meningitis . Plasma 1L-1Ra was elevated in both shock and nonshock patients, extr emely high values being measured in severe shock, High concentrations of IL-1Ra in CSF were found in meningitis. Plasma IL-1Ra peaked shortl y after IL-1 beta and decreased steeply in 1 to 2 days, followed by su stained moderately elevated levels in shock patients, Interestingly, I L-1sRII showed a completely different pattern. At admission, both nons hock and shock patients manifested a similar moderate increase of plas ma IL-1sRII, However, during recovery plasma IL-1sRII further increase d reaching maximal concentrations 3 to 5 days after admission, 1 to 2 days after normalization of IL-1Ra. In shock patients this increase wa s more prominent than in nonshock patients, It is hypothesized that th is increase in plasma IL-1sRII can be explained by a synergistic effec t of dexamethasone and endotoxin, A second interesting observation was that, unlike the pattern in plasma, IL-1sRII levels in CSF paralleled those of IL-1 beta and IL-1Ra. This suggests different modulation of IL-1 beta activity in the subarachnoid space and the plasma compartmen t. We conclude that: (1) During the early stage of meningococcal infec tions IL-1Ra modulates IL-1 activity, whereas during recovery IL-1sRII may be more important. (2) Modulation in CSF and in the plasma compar tment are differentially regulated. (C) 1997 by The American Society o f Hematology.