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.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects*; D002738:Chloroquine / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D003622:Dapsone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015122:Mercaptopurine / Q000494:pharmacology; D008727:Methotrexate / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D013427:Sulfapyridine / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D014747:Vinblastine; D003907:Dexamethasone; D002738:Chloroquine; D003520:Cyclophosphamide; D003622:Dapsone; D015122:Mercaptopurine; D013427:Sulfapyridine; D008727:Methotrexate