Involvement of prostaglandins in the immuno suppression occurring during experimental infection by Paracoccidioides brasiliensis

We investigated whether PGE(2) mediates the immunosuppression observed during Paracoccidioides brasiliensis infection. Con-A-stimulated splenocytes, isolated from mice on days 15 and 60 of infection, release high amounts of PGE(2) this release was inhibited by the treatment of animals with indomethacin, sodium salicylate or meloxicam. The treatment of the animals with salicylate or meloxicam, but not indomethacin, enhanced the release of IL-2 by splenocytes from animals on day 15, but not on day 60 of infection. Furthermore, we demonstrated that the productions of TNF-alpha, IFN-gamma, IL-4, and IL-10 by Con-A-stimulated splenocytes from mice at 15 days of infection were inhibited by treatment with salicylate or meloxicam. Indomethacin inhibited only TNF-alpha and IFN-gamma production. The three treatments caused reduction of granuloma areas in the liver and lungs of infected mice. In conclusion, results suggest that the PGE(2) released by COX-2 mediates the immunosuppression early on (day 15), but not during the later phase (60 days) of P. brasiliensis infection by a mechanism dependent upon IL-4 and IL-10. (C) 2003 Elsevier Science (USA). All rights reserved.