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

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 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) 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.

난치성 다제내성 폐결핵에서 피하주사 Interferon-gamma 치료의 효과: 예비연구

연구 배경 : IFN-${\gamma}$는 결핵에 대한 방어기전에서 가장 중요한 역할을 하는 사이토카인이다. 최근 일부 다제내성결핵 환자에서 치료제로써 사용되어 왔으나 아직 그 효과는 확실히 알려져 있지 않다. 본 연구는 난치성 다제내성폐결핵 환자에서 피하주사 IFN-${\gamma}$의 효과를 알아보기 위하여 시행되었다. 방 법 : 6명의 다제내성폐결핵 환자에서 기존의 항결핵치료를 유지하면서 200만 IU의 IFN-${\gamma}$를 1주 3회, 피하주사하였다. 16주간 치료후 반응이 없으면 치료를 중단하였고, 반응이 있거나 판정이 모호한 경우에는 12주간 더 연장하여 사용하였다. 치료중 4주간격으로 객담 항산균 도말 및 배양검사, 임상상, 및 단순흉부촬영을 시행하였다. 결 과 : 대상환자는 남녀비가 4:2이었고 평균 연령은 37세(15-61)이었다. 5명에서 과거 폐결핵의 기왕력이 있었다. 약제감수성검사상 isoniazid와 rifampicin을 포함하여 평균 6.8(${\pm}1.2$)개의 항결핵약제에 내성을 보였고, IFN-${\gamma}$ 치료 전 10.8개(${\pm}1.3$) 약제를 투여하였다. IFN-${\gamma}$ 치료 28주 후 총 2명에서 균음전되었다. 그러나 IFN-${\gamma}$ 종료후 다시 균배양 양성으로 재발되었다. 모든 환자에서 IFN-${\gamma}$ 피하주사를 종료할 만한 중증 부작용은 관찰되지 않았다. 결 론 : 일부 난치성 다제내성폐결핵 환자에서 피하주사 IFN-${\gamma}$ 병합치료는 균음전 및 치료성공을 유도하였다. 추후 최적 용량, 치료기간, 투여경로, 및 반응의 예측인자를 찾기 위한 연구가 진행되어야 할 것으로 사료된다.