ENHANCEMENT OF LEISHMANICIDAL ACTIVITY OF HUMAN MACROPHAGES AGAINST LEISHMANIA-MAJOR AND LEISHMANIA-DONOVANI INFECTION USING RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

The in vitro effect of recombinant human Granulocyte Macrophage Colony Stimulating Factor (rh-GMCSF) on the leishmanicidal activity and supe roxide anion productivity of macrophages derived from human blood mono cytes (MOs) were investigated. MOs treated with 25, 125, or 250 U/mL o f rh-GMCSF for 72 h prior to infection with leishmania parasites, mani fested significant dose-dependent increase in its leishmanicidal activ ities against Leishmania major and Leishmania donovani parasites. The percentage of increase in leishmanicidal activity of L. major-infected MOs were 22.71, 64.34 and 81.34, respectively while in L. donovani-in fected MOs, it reached 3.01, 32.28 and 74.38, respectively. Treatment of leishmania-infected MOs with rh-GMCSF (250 U/mL) for different peri ods of time up to 96 hours, induced a significant time-dependent reduc tion in the percentage of infected cells and the parasitic load (No. o f amastigotes/100 MOs). After 96 h of treatment with rh-GMCSF, the per centages of reduction in the infection rates were 82.45 in L. major-in fected MOs (p < 0.001) and 39.65 in L. donovani-infected cells (p < 0. 01). The percentage of reduction in the parasitic load reached 90.82 ( p < 0.001) and 36.6 (p < 0.05) in MOs infected with L. major and L. do novani, respectively. The priming effect of rh-GMCSF on superoxide ani on production by human MOs stimulated with phorbol myristate acetate ( PMA) was both dose-dependent and time-dependent. In 72 hour-old human MOs, the maximum superoxide anion release was generated by MOs primed for 45 min with 500 U/mL of rh-GMCSF. These cells produced 8.960 +/- 2 .075 nmol/5 x 10(4) MOs/ 180 min as compared to 4.563 +/- 1.773 nmol/5 x 10(4) unprimed cell control/180 min (p < 0.001).