[A preliminary study on immune adjunctive therapy for multidrug-resistant Mycobacterium tuberculosis infection in animal models].

ABSTRACT

OBJECTIVE: To investigate the effect of adjunctive therapy by immune agents in mice infected with multidrug-resistant tuberculosis (MDR-TB). METHODS: Sixty-eight adult male BALB/c mice were infected with multidrug-resistant Mycobacterium tuberculosis (MTB) by aerosol route. The mice were randomly divided into a control group, an immuno-treatment group, a drug treatment group and a combination treatment group (drug plus immuno-treatment). In each treatment group, 16 mice were treated at day 21 after infection, and another 4 mice were sacrificed at day 21 after infection (treatment for 0 week) as the blank control group. In the treatment group, 4 mice were sacrificed in turn at the day after treatment for 4, 8, 16 and 20 weeks. Lung and spleen mass index at the day after treatment for 8, 16 and 20 weeks, lung and spleen live bacterial count in each period, serum IFN-γ and IL-10 levels at the day after treatment for 8 weeks were measured. Comparisons of analyzed parameters among groups were performed with the one way ANOVA test, and comparisons of parameters between 2 groups were performed with SNK and Games-Howell test. RESULTS: The lung mass index in the immuno-treatment group (0.66 ± 0.09)%, drug group (0.60 ± 0.07)% and combination therapy group (0.57 ± 0.05)% at the day after treatment for 8 weeks were significantly lower than that of the control group (0.81 ± 0.09)%, (F = 7.364, P < 0.01). Spleen CFU of immuno-treatment group at 16 and 20 weeks [(3.11 ± 0.14) lg CFU and (3.15 ± 0.18) lg CFU] were significantly lower than those of the control group [(3.77 ± 0.35) lg CFU and (4.31 ± 0.06)] (F values were 446.424 and 2107.689, P < 0.01). Spleen tissues of the drug group and the combination therapy group were sterile from 4 weeks. The serum IFN-γ levels of immuno-treatment group, drug group and combination therapy were (5.3 ± 1.9) ng/L, (1.3 ± 0.5) ng/L and (0.9 ± 1.3) ng/L, respectively, being significantly lower than that of the control group (10.3 ± 2.1) ng/L (F = 32.128, P < 0.01). The lung and spleen mass index, lung and spleen CFU, serum IFN-γ and IL-10 between medication group and combination therapy showed no significant differences. CONCLUSIONS: Immuno-treatment could mitigate lung tissue inflammation, reduce the number of MTB in mouse spleen tissues and decrease serum IFN-γ levels in the MDR-TB mouse model. However immuno-treatment failed to reduce the number of MTB in lung tissues. There was no adjunctive effect of immuno treatment for MDR-TB mice in reducing the number of MTB and mitigating inflammation.