Inoculation of bacille calmette guerin combined with intraperitoneal adenosine injection enhances antibacterial effect of macrophage against Mycobacterium tuberculosis in mice

Abstract

The protection rate of inoculation with BCG vaccine is only 50 percent, and most of patients with tuberculosis had a history of BCG vaccine inoculation. Adenosine (ADO) has an immunomodulating effect; it promotes immune reaction by increasing number of macrophage and enhancing phagocytosis. The present study was designed to investigate if combined use of adenosine with BCG enhances the anti-Mycobacterium tuberculosis effect of macrophage in mice. Fifty BALB/C mice were divided randomly into 3 groups: BCG group (n = 21), BCG plus ADO group (n = 21) and control group (n = 8). The mice in BCG and BCG plus ADO groups were inoculated with 0.1 ml BCG intradermally and the mice in BCG plus ADO group were injected intraperitoneally with ADO 30 mg/(kg.d) for 5 days. The mice in BCG group and control group were injected with NS 0.1 ml/d for 5 days. Six weeks after the last injection, all mice were challenged with intravenous 1 x 10(6) CFU human Mycobacterium tuberculosis virulent strain. After challenging, lung and spleen specimens were taken at the 10th, 20th and 30th days from the mice of BCG and BCG plus ADO groups and at the 30th day from mice in control group. The pathological examinations of lung and spleen sections were performed after HE staining and acid-fast staining, and detection of cell apoptosis was also performed. Consolidation with neutrophil infiltration was found in most of the lung tissue taken at the day 30; there were a lot of tuberculous granulomas and Mycobacterium tuberculosis in the lungs of control group. The alveolar septum in BCG gradually became wide and in interstitium lymphocyte infiltration dominated, and there were less tuberculous granulomas but there were large number of Mycobacterium tuberculosis in the lungs from 10th to 30th days after challenging. The widening of alveolar septum and consolidation of lung tissue in BCG plus ADO group became milder with monocytes infiltration, and there were few tuberculosis granulomas and Mycobacterium tuberculosis in the lungs from 10th to 30th days after challenging. ADO could increase the number of monocyte-macrophages and promoted anti-bacterial effects of these cells.