Human IL-1 receptor antagonist partially suppresses LPS fever but not plasma levels of IL-6 in Fischer rats.
A human recombinant interleukin-1 receptor antagonist (IL-1ra) recognizes the two known IL-1 receptors and blocks the binding and many biological effects of both IL-1 alpha and IL-1 beta. The effectiveness of IL-1ra in modifying the fever and plasma IL-6 responses elicited by lipopolysaccharide (LPS) in vivo was tested in Fischer 344 rats. Animals that received IL-1ra 0.5 mg/kg intraperitoneally followed 10 min later by 10 micrograms/kg of LPS displayed significantly lower mean fever responses 2-4 h after injection than rats that received vehicle and LPS (0.48 +/- 0.13 vs. 0.95 +/- 0.16 degrees C, P = 0.016). Plasma levels of IL-6 at 4 h after injection were not different in IL-1ra-treated rats compared with controls (407,725 vs. 729,169 U/ml). Based on our previous finding that preadministration of antiserum to IL-1 beta markedly suppressed plasma IL-6 after LPS, and recent evidence that molar excesses of IL-1ra blocked IL-1-induced circulating IL-6 levels, the possibility that IL-1 is responsible for the induction of bioactive IL-6 during inflammation cannot be ruled out. Similarly, the inability of the IL-1ra to completely suppress the febrile responses of rats to LPS in the present study may be dose related. Alternatively, the induction of bioactive IL-6 by IL-1 in the rat may be mediated primarily through some receptor other than the type I (e.g., the type II receptor).
Smith
B K
BK
School of Nursing, University of Michigan, Ann Arbor 48109.
Kluger
M J
MJ
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000627:therapeutic use*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D012795:Sialoglycoproteins