关键词: 结核, 抗多种药物性/药物疗法, 干扰素&, gamma, 小鼠

Abstract: Objective To study the therapeutic effect and immunological mechanism of recombinant human interferon γ (rh-IFN-γ) in treating the mice with multidrug-resistant tuberculosis (MDR-TB). Methods Seventy-two adult male Balb/c mice were infected with multidrug-resistant Mycobacterium tuberculosis via aerosol. Four mice were sacrificed at second day after infection to determine the colony forming units (CFUs) implanted in the lungs. Four mice were sacrificed at 21- day post infection (0 week of treatment). The remaining 64 mice were randomly divided into control group，rh-IFN-γ group，moxifloxacin group and combination therapy group (moxifloxacin+rh-IFN-γ)，16 mice in each group，and started to give medicine treatment at 0 week of treatment．Four mice per group were sacrificed at 4-, 8-, 16- and 20- weeks of treatment, to observe the mass index and live bacteria counting (CFUs) of lung and spleen at each time-point，and to detect the levels of IFN-γ and IL-10 in sera at 8 weeks of treatment．Comparison between the two groups used t test．Comparison among groups were tested by One-Way analysis of variance (ANOVA)，comparison in pairs within group used SNK method and Games-Howell method.  Results Lung and spleen mass index：the lung mass index of moxifloxacin group （5.99±0.72）at 8 weeks were significantly lower than that of control group（8.01±0.91）（F=6.28，P<0.01）．The spleen mass index of moxifloxacin group（2.87±0.15） at 8 weeks were significantly lower than that of control group （3.87±0.41）（F=8.37，P<0.01）． Lung and spleen CFUs： the lung CFUs of moxifloxacin group ［(4.37±0.20)lg/ml］ and combination therapy group ［(4.35±0.18)lg/ml］ at 4 weeks respectively were significantly lower than that of control group ［(5.30±0.21)lg/ml］ and rh-IFN-γ group ［(5.29±0.13)lg/ml］（F=35.55，P<0.01），the lung CFUs of moxifloxacin group ［(2.86±0.29)lg/ml］ and combination therapy group ［(2.63±0.08)lg/ml］ at 8 weeks respectively were significantly lower than that of control group ［(5.00±0.23)lg/ml］ and rh-IFN-γ group ［(4.82±0.55)lg/ml］（F=56.83，P<0.01），and were sterile from 16 weeks (without the growth of Mycobacterium tuberculosis)．Spleen CFUs of rh-IFN-γ group ［(3.21±0.40)lg/ml］ at 20 weeks were significantly lower than that of control group ［(4.31±0.06)lg/ml］（t=5.45，P<0.01）．Spleen tissue of moxifloxacin group and combination therapy group were sterile from 4 weeks．IFN-γ and IL-10 levels in the sera at 8 weeks：the serum IFN-γ levels of rh-IFN-γ group ［（3.40±0.64）ng/L］, moxifloxacin group ［（1.32±0.53）ng/L］ and combination therapy ［（0.47±0.44）ng/L］ were significantly lower than that of control group ［（10.34±2.09）ng/L］（F=55.973，P<0.01）， the serum IFN-γ levels of moxifloxacin group and combination therapy group respectively were obviously lower than that of rh-IFN-γ group（F=55.973，P<0.01）; the serum IL-10 levels had no significant difference among control group ［（6.68±1.30）ng/L］，rh-IFN-γ group ［（9.76±3.97）ng/L］，moxifloxacin group ［（8.74±4.48）ng/L］ and combination therapy group ［（21.34±17.58）ng/L］（F=2.013，P>0.05）. ConclusionRh-IFN-γ can reduce the number of Mycobacterium tuberculosis in splenic tissue and lowered serum IFN-γ levels of MDR-TB mice，but had no significant effect on reducing the number of Mycobacterium tuberculosis and the inflammation in lung tissue of MDR-TB mice．Rh-IFN-γ in combination with moxifloxacin had also no auxiliary role on the treatment of MDR-TB, and on reducing bacteria loads and inflammation of organs in mice.

Key words: Tuberculosis, multidrug-resistant/drug therapy, Interferon-gamma, Mice