EFFECT OF IMMUNOSUPPRESSIVE AND ANTI-INFLAMMATORY DRUGS ON MONOCYTE FUNCTION INVITRO

Abstract

MNL [monocyte] cellular chemotaxis, bacterial killing and phagocytosis, and Oil Red O phagocytosis were studied in vitro in the presence of 8 anti-inflammatory or immunosuppressive drugs. Inhibition of Boyden Chamber migration of MNL in a MNL-lymphocyte mixture was achieved after 1/2 h incubation by 10-3 and 10-4 M concentrations of chloroquine (maximum inhibition 63% .+-. 2.8), dexamethasone (58% .+-. 8.6), 6-mercaptopurine (62% .+-. 4.2), methotrexate (66% .+-. 6.4) and vinblastine (100%). Bacterial killing was not significantly affected by any of the drugs studied. Bacterial phagocytosis was improved by vinblastine at 10-3 and 10-4 M and by 6-mercaptopurine at 10-5 M, but there was apparent interference with the assay at high drug concentrations. Modification of the Oil Red O technique showed inhibitions of MNL phagocytosis by vinblastine at 10-3 M (69% .+-. 2.8 inhibition), chloroquine at 10-3 M (49% .+-. 8.5) and mercaptopurine at 10-3 M (32.5% .+-. 0.7). Cyclophosphamide, although reported to require hepatic conversion in vivo, may be partially activated in a lymphocyte-MNL mixture in vitro, producing a decrease in cell viability but no statistically significant impairment of MNL function. Direct inhibition of MNL cellular function is probably one of the mechanisms of the anti-inflammatory action of chloroquine, dexamethasone, methotrexate, 6-mercaptopurine and vinblastine.