The Pattern of Interleukin-1β (IL-1β) and Its Modulating Agents IL-1 Receptor Antagonist and IL-1 Soluble Receptor Type II in Acute Meningococcal Infections

Abstract

Interleukin-1β (IL-1β) 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-course of IL-1β and these modulating agents in 59 patients with acute meningococcal infections, the prototype human disease of acute endotoxin exposure. Plasma IL-1β was increased only in severe shock and normalized within 12 to 24 hours, indicating that patients were admitted in an early stage of cytokine activation. Increased IL-1β values in cerebrospinal fluid (CSF ) were confined to patients with meningitis. Plasma IL-1Ra was elevated in both shock and nonshock patients, extremely high values being measured in severe shock. High concentrations of IL-1Ra in CSF were found in meningitis. Plasma IL-1Ra peaked shortly after IL-1β and decreased steeply in 1 to 2 days, followed by sustained moderately elevated levels in shock patients. Interestingly, IL-1sRII showed a completely different pattern. At admission, both nonshock and shock patients manifested a similar moderate increase of plasma IL-1sRII. However, during recovery plasma IL-1sRII further increased reaching maximal concentrations 3 to 5 days after admission, 1 to 2 days after normalization of IL-1Ra. In shock patients this increase was more prominent than in nonshock patients. It is hypothesized that this increase in plasma IL-1sRII can be explained by a synergistic effect of dexamethasone and endotoxin. A second interesting observation was that, unlike the pattern in plasma, IL-1sRII levels in CSF paralleled those of IL-1β and IL-1Ra. This suggests different modulation of IL-1β activity in the subarachnoid space and the plasma compartment. We conclude that: (1) During the early stage of meningococcal infections IL-1Ra modulates IL-1 activity, whereas during recovery IL-1sRII may be more important. (2) Modulation in CSF and in the plasma compartment are differentially regulated.

Extracellular and intracellular decoys in the tuning of inflammatory cytokines and Toll-like receptors: the new entry TIR8/SIGIRR

“…Alterations of tissue or body-fluid levels of IL-1RII have been detected in diverse pathological conditions. Increased blood levels of IL-1RII have been detected in experimental endotoxemia, sepsis, acute meningococcal infection, and in patiens treated with IL-2, aspirin, or GC [17][18][19][20][21][22][23]. Recent results suggest that levels of IL-1RII may serve as a readout of the activation of endogenous, anti-inflammatory pathways, for instance, by GC hormones [24,25].…”

Brain cytokines and disease

“…However, the temporal profile of cytokine induction can reflect the stage of cytokine activation, e.g. patients with meningitis consistently exhibit increased IL‐1β levels in the cerebrospinal fluid (96). In this report, unlike the pattern in plasma, IL‐1‐soluble RII levels in the cerebrospinal fluid paralleled those of IL‐1β and IL‐1Ra.…”

“…Based on the different data sets, Van Deuren et al. proposed a different modulation of IL‐1β activity in the subarachnoid space relative to the plasma compartment, and that during the early stage of meningococcal infections IL‐1Ra modulates IL‐1 activity, while during recovery IL‐1 soluble RII may take a more prominent role (96).…”

Treatment with granulocyte colony‐stimulating factor increases interleukin‐1 receptor antagonist levels during engraftment following allogeneic stem‐cell transplantation

“…Our results further indicated an association of increased IL-1ra plasma concentrations with low CRP serum concentrations and, hence, an alleviated acute-phase response in patients treated with G-CSF. IL-1ra is frequently detected in infectious conditions and excessively high IL-1ra levels are detected in blood of patients with bacterial sepsis [56].…”