The Adjuvant Effect of Subcutaneous Interferon-gamma in the Treatment of Refractory Multidrug-resistant Pulmonary Tuberculosis

Kim, Eun Kyung; Shim, Tae Sun; Lee, Jung Yeon; Oh, Yeon Mok; Lim, Chae Man; Lee, Sang Do; Koh, Younsuck; Kim, Dong Soon; Kim, Won Dong; Kim, Woo Sung

Abstract

BACKGROUND: Interferon-gamma (IFN-gamma) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-gamma has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-gamma. This study was performed to examine the effect of subcutaneous IFN-gamma in the treatment of MDR-TB patients.
METHODS
Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-gamma was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-gamma therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period.
RESULTS
The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (+/-1.2) agents including isoniazid and rifampicin. An average of 10.8 (+/-1.3) antituberculous drugs were prescribed before IFN-gamma therapy. The culture became negative in 2 patients (33%) after initiating IFN-gamma therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-gamma therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis.
CONCLUSION
Even though 28 weeks of subcutaneous IFN-gamma therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-gamma therapy. This suggests that subcutaneous IFN-gamma therapy may have suppressive effect on tuberculosis only during the IFN-gamma therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-gamma therapy.