Antituberculosis Treatment: Increasing Evidence for Drug Effects on Innate Cellular Immunity

Over the past several years we have gathered increasing evidence suggestive of direct effects of one or more of the currently used antituberculosis (TB) drugs on various immune parameters in patients with pulmonary TB. Throughout the studies, the standard regimen for treatment of tuberculosis consisted of rifampin, isoniazid, pyrazinamide, and ethambutol given for 2 months during the intensive phase of treatment followed by isoniazid and rifampin given for 4 months. The mean duration of anti-TB treatment at the time of blood collection from patients did not differ significantly between the TB and human immunodeficiency virus-infected TB (HIV/TB) groups in any of the studies. Some of the effects on neutrophil function and receptor expression were contrary to what one might expect given that the resolution of active TB would be associated with recovery of function and normalization of receptor expression. Most of this evidence is inferred from crosssectional studies conducted on TB patients, with only some support from longitudinal data. The primary objective in all of these studies was not the evaluation of the role of anti-TB treatment, and findings reported with respect to drug treatment were incidental to the hypothesis being tested in each individual study. Nonetheless, the findings highlight some important issues that deserve consideration.