Regulatory effect of PGE(2) on microbicidal activity and inflammatory cytokines in canine leishmaniasis

Canine leishmaniasis (CanL) is caused by the intracellular parasite Leishmania infantum. Prostaglandin E2 (PGE(2)) exerts potent regulatory effects on the immune system in experimental model Leishmania infection, but this influence has not yet been studied in CanL. In this study, PGE(2) and PGE(2) receptor levels and the regulatory effect of PGE(2) on arginase activity, NO2, IL-10, IL-17, IFN-gamma, TNF-alpha and parasite load were evaluated in cultures of splenic leucocytes obtained from dogs with CanL in the presence of agonists and inhibitors. Our results showed that splenic leucocytes from dogs with CanL had lower EP2 receptor levels than those of splenic leucocytes from healthy animals. We observed that NO2 levels decreased when the cells were treated with a PGE(2) receptor agonist (EP1/EP2/EP3) or COX-2 inhibitor (NS-398) and that TNF-alpha, IL-17 and IFN-gamma cytokine levels decreased when the cells were treated with a PGE(2) receptor agonist (EP2) or PGE(2) itself. The parasite load in splenic leucocyte cell cultures from dogs with CanL decreased after stimulation of the cells with PGE(2). We conclude that Leishmania infection of dogs modulates PGE(2) receptors and speculate that the binding of PGE(2) to its receptors may activate the microbicidal capacity of cells. (AU)