Vol. 304, Issue 1, 102-108, January 2003

Antinociceptive Effects of Interleukin-4, -10, and -13 on the Writhing Response in Mice and Zymosan-Induced Knee Joint Incapacitation in Rats

Mariana L. Vale, Jaciara B. Marques, Camila A. Moreira, Francisco Aírton C. Rocha, Sérgio H. Ferreira, Stephen Poole, Fernando Q. Cunha and Ronaldo A. Ribeiro

Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil (M.L.V., J.B.M., C.A.M., F.A.C.R., R.A.R.); Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Sao Paolo, Brazil (S.H.F., F.Q.C.); and Endocrinology Section, National Institute for Biological Standards and Control, London, United Kingdom (S.P.)

The antinociceptive effects of interleukin (IL)-4, -10, and -13 were investigated in two different experimental pain models. Our results showed that pretreatment (30 min) with IL-4 (1-5 ng/animal), IL-10 (0.4-10 ng/animal), or IL-13 (0.4-2.5 ng/animal) inhibited the writhing response induced by the i.p. administration of acetic acid (53-89%) or zymosan (63-74%) in mice, and the knee joint incapacitation induced by i.a. injection of zymosan (49-66%) in rats. Neither of the cytokines affected the pain elicited in mice using the hot-plate test. This analgesic effect of IL-4, -10, and -13 was not reversed by the combined pretreatment with the opioid receptor antagonist naloxone. IL-4, -10, or -13 significantly inhibited the release of both tumor necrosis factor (TNF)- (60, 53, and 100%, respectively) and IL-1 (80, 100, and 100%, respectively) by mice peritoneal macrophages obtained after local (i.p.) injection of zymosan. Antisera against IL-4, -10, and -13 potentiated both the zymosan-induced writhing response and the articular incapacitation. Our results demonstrate that IL-4, -10, and -13 display analgesic activity that is probably not due to endogenous opioid release. This analgesic effect could be related to a peripheral mechanism, probably via the inhibition of the release of the pro-inflammatory cytokines TNF- and IL-1 by resident peritoneal macrophages.