Ex vivoevidence for PGE2and LTB4involvement in cutaneous leishmaniasis: relation with infection status and cytokine production

Abstract

SUMMARYEx vivoculture of spleen cells from BALB/c mice infected with 2 × 106Leishmania major(L.major) promastigotes were cultured with ConcanavalinA (ConA) or leishmanial antigen (L. Ag) and tested for prostaglandin E2(PGE2) and for leukotriene B4(LTB4), in order to study their involvement in the evolution of cutaneous leishmaniasis and the connexion with lymphokine-mediated responses. The data were compared with those obtained in BALB/c mice protected againstL. majorby sublethal irradiation (550 rad; cured mice). In the unprotected BALB/c mice the levels of PGE2that were responsible for the depression of interferon-γ (IFN-γ) and tumour necrosis factor-α (TNFα) Th1-associated cytokines and for the relative increase in the interleukin-4 (IL-4) became higher and higher as the lesion progressed. On the contrary, the cured mice produced levels of PGE2similar to normal uninfected controls, high levels of TNFα and IFN-γ and low levels of IL-4. Elevated levels of LTB4were detected in the early stage of infection in the unprotected mice compared to cured ones, a sign of more intense inflammation and a stimulus for the recruitment of inflammatory cells. The observation that exogenous LTB4was able to enhance in vitro both Th1cytokines in cured mice and Th2cytokines in unprotected ones suggests that LTB4could act in the recruitment of the T cells already committed to Th1or Th2phenotype.