INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA BY LEISHMANIA-INFANTUM IN MURINE MACROPHAGES FROM DIFFERENT INBRED MICE STRAINS

The present study was undertaken to determine whether the viscerotropic species, Leishmania infantum, endemic in Italy, could induce tumor necrosis factor α (TNFα) in murine macrophages. Genetically susceptible (Lshs) and resistant (Lshr) mice were used in the attempt to correlate TNFα production with the ability to control parasite growth and replication. Resident peritoneal macrophages of C3H/HeN, DBA/2, CBA (Lshr), C57BL/10 and BALB/c (Lshs) mice were infected in vitro with promastigotes at a parasite to cell ratio of 8:1. No significant differences in the percentages of infected peritoneal cells of Lshs versus Lshr mice were observed until 72 h of in vitro culture. On the contrary, Kupffer cells from Lshr mice inhibited Leishmania replication. Peritoneal macrophages of resistant mice produced significantly higher amounts of TNFα as compared to susceptible mice. TNFα production of both resistant and susceptible mice peaked at about 5 h after the challenge with the parasite. No TNFα was found in supernatants of infected Kupffer cells from all the strains tested. The ability of macrophages from susceptible or resistant mice strains to produce TNFα after challenge with Leishmania infantum does not seem related to their capacity to control parasite replication in vitro. © 1992.