Immune responses and immunostimulation in tuberculosis therapy.

Despite a reasonably extensive literature on cellular and humoral immune responses in tuberculous disease, abnormalities tend to be secondary rather than predisposing to disease. No discrete immune deficiency or failure, which would explain the progression from non-infection to infection with Mycobacterium tuberculosis to tuberculous disease, has been identified. There is evidence that tuberculous disease occurs in a spectrum, analogous to leprosy, and it would seem that if immunostimulants, as adjuncts to standard therapy, are to be of any value in the treatment of tuberculosis, they should be used for non-reactive tuberculosis patients. The range of immunostimulants currently available tends to be indiscriminate in action and their targets in tuberculous disease largely uncertain; their role in therapy in discussed.

Effects of clofazimine alone or combined with dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy.

The effects of clofazimine on neutrophil activities such as random motility, migration to the leukoattractants endotoxin-activated serum and N-formyl-L-methionyl-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.

In vitro and in vivo effects of dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy.

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 vivo. Dapsone had no effect on postphagocytic hexose monophosphate shunt activity in vivo. Similar 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 lymphocyte transformation at high concentrations in vitro, but had slight stimulatory activity on phytohemagglutinin-induced transformation in controls and patients in vivo.