EX-VIVO EVIDENCE FOR PGE(2) AND LTB(4) INVOLVEMENT IN CUTANEOUS LEISHMANIASIS - RELATION WITH INFECTION STATUS AND CYTOKINE PRODUCTION

Ex vivo culture of spleen cells from BALB/c mice infected with 2 x 10( 6) Leishmania major (L. major) promastigotes were cultured with Concan avalinA (ConA) or leishmanial antigen (L. Ag) and tested for prostagla ndin E(2) (PGE(2)) and for leukotriene B-4 (LTB(4)), 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 against L. major by suble thal irradiation (550 rad; cured mice). In the unprotected BALB/c mice the levels of PGE(2) that were responsible for the depression of inte rferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF alpha) Th-1-associated cytokines and for the relative increase in the interle ukin-4 (IL-4) became higher and higher as the lesion progressed. On th e contrary, the cured mice produced levels of PGE(2) similar to normal uninfected controls, high levels of TNF alpha and IFN-gamma and low l evels of IL-4. Elevated levels of LTB(4) were detected in the early st age of infection in the unprotected mice compared to cured ones, a sig n of more intense inflammation and a stimulus for the recruitment of i nflammatory cells. The observation that exogenous LTB(4) was able to e nhance in vitro both Th-1 cytokines in cured mice and Th-2 cytokines i n unprotected ones suggests that LTB(4) could act in the recruitment o f the T cells already committed to Th-1 or Th-2 phenotype.