Intracellular replication and lymphokine-induced destruction of Leishmania tropica in C3H/HeN mouse macrophages.

C3H/HeN resident peritoneal macrophages in suspension culture supported continuous replication of L. tropica amastigotes; the total number of intracellular parasites increased 8- to 10-fold over 96 hr in culture. Lymphokine treatment of macrophages markedly affected intracellular replication of the Leishmania. Cultures treated with lymphokines before exposure to L. tropica were more resistant to infection, and 35% fewer cells contained intracellular amastigotes compared to medium-treated controls. Lymphokine-pretreated cells that became infected also inhibited the replication of intracellular amastigotes. Macrophage cultures treated with lymphokines after infection exhibited potent microbicidal activity; 75 to 80% of macrophages were free of intracellular parasites by 72 hr. Fractionation of lymphokine supernatants by Sephadex G-100 demonstrated 3 areas of activity for the induction of macrophage intracellular killing (130,000, 45,000, less than or equal to 10,000 daltons); one of these activity peaks (45,000-m.w. lymphokine(s)) also induced increased resistance to infection with L. tropica.