Cytokine-mediated inflammatory hyperalgesia limited by interleukin-1 receptor antagonist.
1. The effect of IL-1ra on response to intraplantar (i.pl.) injection of LPS, carrageenin, bradykinin, TNFalpha, IL-1beta, IL-8, PGE(2) and dopamine was investigated in a model of mechanical hyperalgesia in rats. 2. IL-1ra inhibited hyperalgesic response to LPS, carrageenin, bradykinin, TNFalpha, and IL-1beta, but not responses to IL-8, PGE(2) and dopamine. 3. A sheep anti-rat IL-1ra serum potentiated response to LPS, carrageenin, bradykinin, TNFalpha and IL-1beta but not IL-8. 4. Carrageenin and LPS stimulated and production of immunoreactive TNFalpha, IL-1beta and IL-1ra in the skin of injected paws. 5. The inhibition by IL-1ra of the hyperalgesic response to carrageenin was not affected by antibodies neutralizing IL-4 and IL-10. 6. In mice, IL-1ra inhibited the nociceptive response to i.p. injection of acetic acid. 7. These data suggest that IL-1ra, released at sites of inflammation, limits inflammatory hyperalgesia. This effect is independent of (IL-1ra-induced) IL-4 and IL-10 and appears to be the result of antagonism by IL-1ra of IL-1beta-stimulated eicosanoid production.
Cunha
J M
JM
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Cunha
F Q
FQ
Poole
S
S
Ferreira
S H
SH
D019342:Acetic Acid / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002351:Carrageenan / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb; D006930:Hyperalgesia / Q000378:metabolism / Q000517:prevention & control*; D007106:Immune Sera / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D016209:Interleukin-8 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep; D012795:Sialoglycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D000906:Antibodies; D016207:Cytokines; C507764:Il1rn protein, mouse; D007106:Immune Sera; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D002351:Carrageenan; D015232:Dinoprostone; D019342:Acetic Acid; D001920:Bradykinin; D004298:Dopamine