title: The pattern of interleukin-1beta (IL-1beta) and its modulating agents IL-1 receptor antagonist and IL-1 soluble receptor type II in acute meningococcal infections.
abstract: Interleukin-1beta (IL-1beta) 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-1beta and these modulating agents in 59 patients with acute meningococcal infections, the prototype human disease of acute endotoxin exposure. Plasma IL-1beta 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-1beta 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-1beta 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-1beta and IL-1Ra. This suggests different modulation of IL-1beta 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.
authors.affiliation: Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Deuren
authors.forename: J
authors.initials: J
authors.lastname: van der Ven-Jongekrijg
authors.forename: E
authors.initials: E
authors.lastname: Vannier
authors.forename: R
authors.initials: R
authors.lastname: van Dalen
authors.forename: G
authors.initials: G
authors.lastname: Pesman
authors.forename: A K
authors.initials: AK
authors.lastname: Bartelink
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D008297:Male; D008585:Meningitis, Meningococcal / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008589:Meningococcal Infections / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D053574:Receptors, Interleukin-1 Type II; D012772:Shock, Septic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D004731:Endotoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins; D003907:Dexamethasone