Dynamics of cytokine generation in patients with active pulmonary tuberculosis.

Abstract

Cytokines have been implicated in the protective immunity, pathophysiology and development of tuberculosis. Most people who become infected with Mycobacterium tuberculosis mount an effective protective immune response, but 5-10% develop disease. Active pulmonary tuberculosis can be considered to reflect an ineffective immune response against mycobacterial infection. A better understanding of how cytokine production contributes to immunity and pathology would aid the development of new vaccines and therapeutic strategies. At the time of diagnosis, production of M. tuberculosis or mycobacterial antigen-induced interferon-gamma by peripheral blood mononuclear cells from tuberculosis patients is usually depressed, compared with that of healthy control subjects, whereas cytokine production at the site of disease is elevated. In most patients, depressed interferon-gamma production by peripheral blood mononuclear cells seems to be a transient response because it is significantly increased in most active tuberculosis patients during and following successful antituberculous therapy. However, some patients remain anergic in vivo and in vitro after chemotherapy, and the underlying biochemical mechanisms for T cell anergy in modulating protection or pathology in tuberculosis needs further clarification. Among the cytokines contributing to protective immunity, interleukins 12 and 18, and tumour necrosis factor-alpha are important, the basis of recent studies with tuberculosis patients. A more complete understanding of cytokine dynamics in individual cells in active pulmonary tuberculosis patients will provide further knowledge about immunopathogenesis and protective immunity in human tuberculosis. This should ultimately enhance development of preventive and therapeutic strategies against this enormously successful intracellular pathogen.