Cytokine-mediated inflammatory hyperalgesia limited by interleukin-13.
The effect of interleukin-13 (IL-13) on hyperalgesic responses to intraplantar (i.pl.) injection of carrageenin, E. coli endotoxin (LPS), bradykinin, tumour necrosis factor a (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-8 (IL-8) and prostaglandin E(2) (PGE(2)) was investigated in a model of mechanical hyperalgesia in rats. Also, the cellular source of the IL-13 was investigated. IL-13, administered 30 min before the stimulus, inhibited responses to carrageenin, LPS, bradykinin, and TNF-alpha, but not responses to IL-1 beta, IL-8 and PGE2. IL-13, administered 2 hours before the injection of IL-1b, did not affect the response to IL-1b, whereas IL-13, administered 12 hours or 12 + 2 hours before the IL-1 beta, inhibited the hyperalgesia (- 35%, - 77%, respectively). In murine peritoneal macrophages, IL-13 administered 2 hours before stimulation with LPS, inhibited the production of IL-1 beta (- 67%) and PGE(2) (- 56%). IL-13 administered 12 hours before stimulation with LPS inhibited LPS-stimulated PGE(2) but not IL-1 beta. An anti-IL-13 serum potentiated responses to carrageenin, LPS, bradykinin and TNF-alpha (but not IL-1 beta and IL-8), as well as responses to bradykinin in rats depleted of mast cells with compound 40/80, but not in athymic rats. These data suggest that IL-13, released by lymphocytes, limits inflammatory hyperalgesia by the inhibition of the production TNF-alpha, IL-1 beta, IL-8 and PGs.
Lorenzetti
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BB
Department of Pharmacology, Institute of Biological Science, Univeridade Federal do Paraná, Brazil.
Poole
S
S
Veiga
F H
FH
Cunha
F Q
FQ
Ferreira
S H
SH
D000818:Animals; D001769:Blood; D001920:Bradykinin / Q000494:pharmacology; D002351:Carrageenan / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D006930:Hyperalgesia / Q000503:physiopathology*; D007106:Immune Sera; D066298:In Vitro Techniques; D018836:Inflammation Mediators; D018793:Interleukin-13 / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D051381:Rats; D011923:Rats, Nude; D017208:Rats, Wistar
D016207:Cytokines; D007106:Immune Sera; D018836:Inflammation Mediators; D018793:Interleukin-13; D008070:Lipopolysaccharides; D002351:Carrageenan; D001920:Bradykinin