The effect of immunosuppressive and anti-inflammatory drugs on monocyte function in vitro

MNL cellular chemotaxis, bacterial killing and phagocytosis, and Oil Red O phagocytosis were studied in vitro in the presence of eight anti-inflammatory or immunosuppressive drugs. Inhibition of Boyden Chamber migration of MNL's in a MNL-lymphocyte mixture was achieved after 1/2 hr incubation by 10(-3) and 10(-4) mol/L. 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. These results support direct inhibition of MNL cellular function as one of the mechanisms of the anti-inflammatory action of chloroquine, dexamethasone, methotrexate, 6-mercaptopurine, and vinblastine.