INHIBITION OF LEISHMANIA GROWTH BUT NOT OF PHAGOCYTIC FUNCTIONS OF MACROPHAGES BY 5-FLUOROURACIL IN-VITRO

We studied the effect of 5-fluorouracil on the growth of two leishmani a strains. A concentration of 20 mu M inhibited over 95% of the growth of 0.5 x 10(5) promastigotes/ml in three days. Growth inhibition near 50% was observed with 2 mu M 5-fluorouracil in three days at cell con centrations ranging from 2.5 x 10(3) to 2.5 x 10(6) cells/ml. A 44 mol ar excess of thymidine protected by 80% from the effect of 5-fluoroura cil, suggesting that leishmania thymidylate synthase is a target for t he compound. The most important changes observed by electron microscop y were in the nucleus. 5-fluorouracil had no apparent toxic effect on macrophage phagocytic functions. The respiratory burst of macrophages was identical with or without 5-fluorouracil and their capacity to ing est erythrocytes was unaltered. Microscopically, the leishmania-macrop hage interaction in vitro showed that with 5-fluorouracil macrophages destroy the protozoan very effectively. In the absence of the drug, le ishmanias thrive inside phagocytic vacuoles of macrophages leading to their progressive destruction.