Abstract
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)-α (60, 53, and 100%, respectively) and IL-1β (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-α and IL-1β by resident peritoneal macrophages.
Footnotes
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This work was supported by the grants from the following Brazilian Foundations: Fundação de Amparo àPesquisa no Estado de São Paulo, Conselho Nacional de Desenvolvimento Cientı́fico e Tecnológico (Pronex), and Coordenação de Aperfeiçoamento de Pessoal de Nı́vel Superior (Procad).
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DOI: 10.1124/jpet.102.038703
- Abbreviations:
- TNF
- tumor necrosis factor
- IL
- interleukin
- COX
- cyclooxygenase
- iNOS
- inducible nitric oxide synthase
- S
- saline
- NT
- nontreated
- Zym
- zymosan
- Ab IL
- antiserum against interleukin
- Received May 14, 2002.
- Accepted September 4, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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