ADJUNCTIVE IMMUNOTHERAPY OF TUBERCULOSIS

Tuberculosis persists as a major infectious disease contributing to si gnificant morbidity and mortality worldwide. Presently, antituberculou s chemotherapy remains the mainstay of control of tuberculosis; howeve r, it is associated with complexities including issues of patient comp liance, drug toxicity, and inadequacy to eradicate all Mycobacterium t uberculosis at sites of infection. Recent understanding of the immunop athogenesis of tuberculosis allows the possible application of adjunct ive immunotherapy to the treatment of tuberculosis. Therapies that wou ld upregulate the host antimycobacterial immune response and/or attenu ate T-cell-suppressive and macrophage-deactivating cytokines may prove to be useful in the treatment of tuberculosis. T helper 1 cytokines, such as interferon gamma, IL-2, and IL-12 through enhancement of T-cel l function and macrophage activation may prove to be potent immunother apeutic agents. On the other hand, agents that inhibit deactivating cy tokines (such as transforming growth factor beta) or reduce the produc tion and effect of pro-inflammatory molecules (such as tumor necrosis factor alpha) may also prove to be useful. Other issues to consider in an immunotherapeutic approach to tuberculosis are the administration of agents locally to sites of Mycobacterium tuberculosis infection, an d employing combinations of agents to modulate the cytokine milieu of the granulomas more effectively. Adjunctive immunotherapy may be parti cularly useful in the management of difficult-to-treat tuberculosis or tuberculosis in the immunodeficient host.