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Cytokine‐mediated inflammatory hyperalgesia limited by interleukin‐10
Author(s) -
Poole S.,
Cunha F.Q.,
Selkirk S.,
Lorenzetti B.B.,
Ferreira S.H.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb14987.x
Subject(s) - bradykinin , hyperalgesia , cytokine , prostaglandin e , endocrinology , prostaglandin e2 , stimulation , tumor necrosis factor alpha , interleukin , medicine , prostaglandin , pharmacology , chemistry , nociception , receptor
1 The effect of interleukin‐10 (IL‐10) upon the hyperalgesic activities in rats of bradykinin, tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), prostaglandin E 2 (PGE 2 ) and carrageenin were investigated in a model of mechanical hyperalgesia. 2 Hyperalgesic responses to bradykinin (1 μg) were inhibited in a dose‐dependent manner by prior treatment with IL‐10 (1–100 ng). 3 Hyperalgesic responses to TNFα (2.5 pg), IL‐1β (0.5 pg) and IL‐6 (1.0 ng) but not to IL‐8 (0.1 ng) and PGE 2 (50 ng and 100 ng) were inhibited by prior treatment with IL‐10 (10 ng). 4 Hyperalgesic responses to carrageenin (100 μg) were inhibited by IL‐10 (10 ng) when this cytokine was injected before but not after the carrageenin. 5 A monoclonal antibody to mouse IL‐10 potentiated the hyperalgesic responses to carrageenin (10 μg) and TNFα (0.025 pg) but not that to IL‐8 (0.01 ng). 6 In in vitro experiments in human peripheral blood mononuclear cells (MNCs), IL‐10 (0.25‐4.0 ng ml −1 ) inhibited in a dose‐dependent manner PGE 2 production by MNCs stimulated with IL‐1β (1–64 ng ml −1 ) or endotoxin (lipopolysaccharide, LPS, 1 iu=143 pg ml −1 ) but evoked only small increases in IL‐Ira production. 7 These data suggest that IL‐10 limits the inflammatory hyperalgesia evoked by carrageenin and bradykinin by two mechanisms: inhibition of cytokine production and inhibition of IL‐1β evoked PGE 2 production. Our data suggest that the latter effect is not mediated via IL‐10 induced IL‐Ira and may result from suppression by IL‐10 of prostaglandin H synthase‐2 (COX‐2).