Effects of cigarette smoke on the administration of isoniazid and rifampicin to macrophages infected with Mycobacterium tuberculosis.

Rodríguez-Fernández, Pablo; Gómez, Andromeda-Celeste; Gibert, Isidre; Prat-Aymerich, Cristina; Domínguez, Jose

BACKGROUND Smoking is a cause behind many diseases, including tuberculosis, and it is a risk factor for tuberculosis infection and mortality. Moreover, smoking is associated with a poor tuberculosis treatment outcome. OBJECTIVES In this study, we focus on the effects of cigarette smoke on an infected cell culture treated with anti-tuberculosis drugs. MATERIALS AND METHODS Cytotoxicity on THP-1, J774A.1 and MH-S cell lines and growth of Mycobacterium tuberculosis exposed to a reference or a commercial cigarette was evaluated. THP-1 cell line was exposed to cigarette smoke, infected with Mycobacterium tuberculosis and treated with anti-tuberculosis drugs. Apoptosis and death cell were also tested on M. bovis BCG infected cells. Minimal inhibitory concentrations of anti-tuberculosis drugs were analyzed. RESULTS All cells lines showed viability values higher than 80% when exposed to cigarette smoke extract. However, THP-1 cell line infected with M. bovis BCG and exposed to Marlboro cigarette smoke showed up to a 54% reduction of apoptotic cells than cells unexposed to smoke. M. tuberculosis exposed to Marlboro cigarette smoke for 11 days had an optical density 16% lower than unexposed bacteria. When cells were infected with M. tuberculosis, the intracellular recovery of CFUs showed up to a 0.66 log reduction in cells exposed to cigarette smoke extract because of a potential impairment in the phagocytosis. Macrophages treated with drugs showed up to a 2.55 log reduction in the intracellular load burden compared with non-treated ones. Despite poor treatment outcome on TB smoker patients, minimal inhibitory concentration of rifampicin increased only 2-fold in M. tuberculosis exposed to cigarette smoke. CONCLUSION Smoking interferes with tuberculosis treatment impairing the immunity of the host.