Adjunctive immunotherapy of tuberculosis.

Abstract

Tuberculosis persists as a major infectious disease contributing to significant morbidity and mortality worldwide. Presently, antituberculous chemotherapy remains the mainstay of control of tuberculosis; however, it is associated with complexities including issues of patient compliance, drug toxicity, and inadequacy to eradicate all Mycobacterium tuberculosis at sites of infection. Recent understanding of the immunopathogenesis of tuberculosis allows the possible application of adjunctive immunotherapy to the treatment of tuberculosis. Therapies that would upregulate the host antimycobacterial immune response and/or attenuate 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-cell function and macrophage activation may prove to be potent immunotherapeutic agents. On the other hand, agents that inhibit deactivating cytokines (such as transforming growth factor beta) or reduce the production 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, and employing combinations of agents to modulate the cytokine milieu of the granulomas more effectively. Adjunctive immunotherapy may be particularly useful in the management of difficult-to-treat tuberculosis or tuberculosis in the immunodeficient host.