Cytokine therapy of tuberculosis at the crossroads

Drug treatment is the key strategy in TB control. However, the treatment course lasts 6-9 months because the current anti-TB drugs are poorly effective against nondividing (i.e., persistent) bacilli. As a result, completion rates are unsatisfactory, leading to emergence and spread of multidrug-resistant infection. It would, therefore, be very desirable to design a form of complementary treatment that could speed up the recovery process for people afflicted with TB and reduce the relapse rates. With the advancement of our understanding of the immunopathogenesis of TB, it has become increasingly possible to develop novel adjunctive immunotherapies for both drug-susceptible and drug-resistant TB. Notably, cytokines probably offer the most promising prospect of such a therapy being introduced in routine clinical practice. However, in many ways, the cytokine therapy of TB has reached a crossroad, since, although the initial promise failed to live up to expectations, sufficient encouraging evidence exists to warrant further exploration. There are clear arguments in favor as well as against such treatments. This review aims to provide a rationale for cytokine treatment of TB, to describe the current status of several cytokines that have been considered for that purpose and, ultimately, to make a case for the need for further clinical trials.