The effect of IL-1RA and IL-13 on cutaneous leishmaniasis in BALB/C mice as to hyperalgesia and the levels of IL-1b and IL-6. (c2005)

Abstract

Recent researches demonstrated the presence of a sustained hyperalgesic state in all BALB/c mice (known to be susceptible to Leishmania major) inoculated with a high dose of Leishmania major (2.5 x 106 promastigotes per hind paw) as shown by the evident decrease in their pain thresholds. However, no neural involvement has been reported to date about role of IL-Ira and IL-13 on Leishmania major-induced inflammation as model. Thus, we aim in this project to prove the hypoalgesic effect of IL-lra and IL-13 by reversing hyperalgesia in BALB/c mice induced by Leishmania major as a new model since other previous studies showed the anti-inflammatory effect of IL-lra and IL-13 using different models (Saade et ai., 2000; Safieh-Garabedian et ai., 1997a; Cunha et ai., 2000). This hyperalgesia should be accompanied with a significant increase in the levels of proinflammatory cytokines IL-l/3 and IL-6 as is the case in the mice injected with a high dose of the parasite (Hirano, 1998; Kanaan et ai., 2000). Both IL-lra and IL-13 had the same effect on IL-l/3 and reduced its levels which indicate its involvement in hyperalgesia directly. This confirms that both IL-lra and IL-13 are hypoalgesic. Alternatively the two former cytokines had different effect on IL-6 which our results showed its indirect effect on hyperalgesia mechanism. IL-lra decreased IL-6 levels while IL-13 increased it. It seems that IL-6 playas a mediator IL-6 to induce hyperalgesia by stimulation of other pro inflammatory and anti-inflammatory cytokines (Dinarello, 1994, 1997).