The effects of dapsone on polymorphonuclear leukocyte functions and lymphocyte mitogen-induced transformation were assessed in vitro and in vivo in normal individuals and in newly diagnosed untreated patients with lepromatous leprosy. The effects of dapsone on the cell-free generation of superoxide by the xanthine:xanthine oxidase system and iodination of bovine serum albumin by horseradish peroxidase were also investigated. In normal individuals dapsone mediated stimulation of polymorphonuclear leukocyte migration in vitro and in vivo. Dapsone had no effects on postphagocytic hexose monophosphate shunt activity or superoxide generation in vitro, but caused slight inhibition of peroxidase-mediated protein iodination in vitro and in vivo and hexose monophosphate shunt activity in vivo. Sirnilar effects were found in patients with lepromatous leprosy. Dapsone also decreased the inhibitory activity of serum from patients with lepromatous leprosy on normal polymorphonuclear leukocyte migration in vitro. Progressive loss of serum-mediated inhibition of migration was observed after ingestion of dapsone by the patients. Further experiments showed that stimulation of polymorphonuclear leukocyte motility was related to inhibition of the peroxidase-H202-halide system in vitro. The drug caused inhibition of lymphocyte transformation at high concentrations in vitro, but had slight stimulatory activity on phytohemagglutinin-induced transformation in controls and patients in vivo.

The effects of clofazimine on neutrophil activities such as random motility, migration to the leukoattractants endotoxin-activated serum and N-formyl-Lmethionyl-L-leucyl-L-phenylalanine phagocytosis of Candida albicans, postphagocytic hexose-monophosphate shunt activity, and myeloperoxidase-mediated iodination and the effects of clofazimine on lymphocyte transformation to mitogens were assessed in vitro and after ingestion of the drug by normal individuals and patients with lepromatous leprosy. For in vitro studies, the concentration range of the drug investigated was 10-6 M to 10-2 M. For in vivo studies, subjects ingested 200 mg of clofazimine daily for a period of 5 days. At concentrations of 5 x 10-6 M to 5 x 10-3 M clofazimine caused a progressive dose-dependent inhibition of neutrophil motility without detectable effects on phagocytosis, postphagocytic hexose-monophosphate shunt activity, or myeloperoxidase-mediated iodination. Over the same concentration range, clofazimine inhibited lymphocyte transformation. The inhibitory effect on neutrophil motility was associated with a spontaneous stimulation of oxidative metabolism and could be prevented by coincubation of dapsone with clofazimine. After ingestion of clofazimine responsiveness of lymphocytes to mitogens was decreased in normal volunteers and leprosy patients; neutrophil motility in normal individuals was likewise inhibited.Clofazimine (5), also known as B663 or Lamprene, is an extensively used anti-leprosy drug. Apart from its anti-mycobacterial activity, clofazimine has also been reported to possess antiinflammatory activity (17). This property enhances the value of clofazimine in leprosy, since it may also be used to control adverse immunological reactions. In this study, we have investigated the effects of clofazimine in vitro and in vivo on the motility, phagocytosis, and postphagocytic metabolic activities of neutrophils and transformation to mitogens of lymphocytes from normal individuals and patients with lepromatous leprosy. The effects of combinations of clofazimine and dapsone on the motility of neutrophils from patients with leprosy have also been investigated.MATERIALS AND METHODS Chemotherapeutic agents. Clofazimine in 100-mg capsules of pure drug was obtained from Ciba-Geigy, Johannesburg. For in vitro studies, the drug was solubilized in dimethyl sulfoxide (DMSO) to give a concentration range of 106 M to 10-3 M (equivalent to 0.3 to 300 j.Lg/ml) in Hanks balanced salt solution (HBSS) for studies of motility, 0.15 M phosphatebuffered saline for phagocytic studies and TC199 for lymphocyte studies. Both HBSS and TC199 were obtained from GIBCO Laboratories, Grand Island, N.Y. Control systems were included for each clofazimine concentration investigated, and these contained the corresponding DMSO concentrations: 0.0015 to 1.5% DMSO for 10-6 M to 10-3 M clofazimine.

The effects of clofazimine on neutrophil motility to endotoxin activated serum and mitogen-in duced lymphocyte transformation of leucocytes from normal individuals in vitro, and after ingestion of clofaz imine by normal adult volunteers have been assesse d. Clofazimine caused a progressive dose-dependent in hibition of neutrophil motility and of lymphocyte transformation in vitro. Ingestion of the drug by normal volunteers was accompanied by decreased neutrophil motility and lympho cyte transformation to mitogens. These fin dings suggest that the anti inflammatory properties of clofazimine are related to inhibition of these cellular immune functions.