title: Immunotherapy using IL-2 and GM-CSF is a potential treatment for multidrug-resistant Mycobacterium tuberculosis.
abstract: This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculosis (TB) infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, IL-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P<0.01) and 0.58 (P<0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P<0.01) and 1.22 (P<0.01) lg CFU, respectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P<0.01). This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis (MDR-TB).
authors.affiliation: State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: YongRong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: QiaoYang
authors.initials: Q
authors.lastname: Xian
authors.forename: LingYun
authors.initials: L
authors.lastname: Shao
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yang
authors.forename: XiaoNing
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000627:therapeutic use*; D007538:Isoniazid / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000401:mortality / Q000628:therapy*
chemical_list: D000904:Antibiotics, Antitubercular; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007538:Isoniazid; D012293:Rifampin