In vitro indomethacin administration upregulates interleukin-12 production and polarizes the immune response towards a Th1 type in susceptible BALB/c mice infected with Leishmania mexicana.

The immune response in Leishmania infected BALB/c mice is associated with a Th2 type cellular response, which has been characterized by the absence of interleukin (IL)-12, interferon (IFN)-gamma, and nitric oxide (NO) and the presence of IL-10 and IL-4. Prostaglandins (PGs) can modulate the immune response inhibiting the development of Th1 response and enhancing the development of Th2 response. We investigated the production of PGs and their effects on cytokine and NO production by spleen cells from Leishmania mexicana infected BALB/c and C57BL/6 mice. Increased production of PGs was noted as early as 1 week after infection in BALB/c mice, whereas in infected C57BL/6 mice PGs were not detected. In vitro administration of indomethacin (INDO), a specific inhibitor of PGs synthesis, reduced PGs production at normal levels, and increased IL-12, IFN-gamma, and NO production in infected BALB/c mice. Whereas, IL-10 and IL-4 were not affected. Moreover, INDO did not modulate cytokine and NO production in infected C57BL/6. INDO addition induced the intracellular killing of parasites in infected BALB/c mice. Together, these results suggest that suppression of PGs by INDO may promote the development of a protective Th1 type response in susceptible mice by a mechanism, which involves an enhancement of IL-12, IFN-gamma and NO production. These findings were confirmed by smaller lesions in BALB/c mice, when treated with INDO.