Role of cytokines in immune response to pulmonary tuberculosis

Immunopathogenesis of tuberculosis needs to be explored in search of a proper vaccine as well as for adjunctive immunotherapy particularly in patients with drug resistant tuberculosis. In tuberculosis, IFN-gamma, a product of T lymphocytes, contributes to protective immunity against M. tuberculosis by activating macrophages to a more effective elimination of these organisms. Interleukin-12 and interleukin-18 are macrophage products that favor the development of Th1 type of protective immune response. Production of these cytokines may not only facilitate granuloma formation and bacillary elimination but may also cause local tissue necrosis and systemic effects such as fever and wasting, due to the release of TNF-alpha into the circulation. The production of anti-inflammatory cytokines such as IL-10, TGF-beta and IL-4 in response to M. tuberculosis may down regulate the immune response and limit tissue injury by inhibiting excessive inflammatory response. These cytokines, if produced in excess, may result in failure to control infection resulting in widely disseminated tuberculosis. It is the balance between the inflammatory and protective immune response that determines the outcome of tuberculosis infection. In that context, increased IFN-y as against reduced TNF-alpha probably suggests a better outcome. Similarly, an effective vaccine has to stimulate a precise combination of T cells and cytokines needed for the many aspects of immune response and a potent immunotherapeutic agent may require to encompass the multiple parameters to be of therapeutic relevance.