Xie Qiangmin, Bian Rulian, Wu Kangsong, Zheng Xing
Zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of China, Medical School of Zhejiang University, Hangzhou 310031, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2002 Aug;25(8):488-92.
To study the inhibitory effect of Mycobacterium vaccae (M. vaccae) on the accumulation of airway inflammatory cells and its regulatory effect on IFN-gamma/IL-4 balance in bronchoalveolar lavage fluids (BALF) from ovalbumin (OVA)-challenged and sensitized mice, therefore to provide experimental evidence for the application of M. vaccae in the treatment of asthma.
Sensitized mice were given a single dose of M. vaccae 3 days before inhaled OVA-challenge by one of the three routes: intramuscularly (i.m.), by intratracheal (i.t) instillation or by cutaneous scarification (c.s). Accumulation of inflammatory cells, IFN-gamma and IL-4 levels in BALF were determined.
The total numbers of the inflammatory cells in BALF from the M. vaccae 2.25 micro g (per mouse) c.s group (6 +/- 6) x 10(8)/L, the 2.25 microgram i.t group (7 +/- 6) x 10(8)/L and the 22.5 micro g i.m group (8 +/- 5) x 10(8)/L, were significantly lower than that of the model control (15 +/- 8) x 10(8)/L (P < 0.05). Eosinophils in the 2.25 microgram c.s group 0.7 +/- 0.5, the 2.25 microgram i.t group 1.6 +/- 1.9, the 7.5 micro g i.m group 2.6 +/- 1.3 and the 22.5 microgram i.m group 1.40 +/- 1.20, were significantly lower than those in the model group 4.90 +/- 4.60 (P < 0.05 and P < 0.01). IFN-gamma levels in the 2.25 microgram c.s group (289 +/- 57) pg/ml, the 2.25 micro g i.t group (335 +/- 57) pg/ml and the 22.5 micro g i.m group (313 +/- 49) pg/ml, were significantly higher than that in the model group (216 +/- 42) pg/ml (P < 0.05 and P < 0.01). IL-4 levels in the 2.25 microgram c.s group (63 +/- 19) pg/ml, the 2.25 microgram i.t group (8 +/- 5) pg/ml and the 22.5 micro g i.m group (13 +/- 6) pg/ml, were significantly lower than that in the model group (93 +/- 25) pg/ml (P < 0.05 and P < 0.01). The inhibitory effect on eosinophil accumulation by i.t or c.s M. vaccae was 10 times stronger than that by i.m M. vaccae. i.t M. vaccae was the most effective in regulating the IFN-gamma/IL-4 ratio.
M. vaccae inhibited airway inflammation via regulating Th1/Th2 balance, suggesting that it may be beneficial in the treatment of asthma.
研究母牛分枝杆菌（M. vaccae）对卵清蛋白（OVA）致敏激发小鼠支气管肺泡灌洗液（BALF）中气道炎症细胞积聚的抑制作用及其对IFN-γ/IL-4平衡的调节作用，为M. vaccae应用于哮喘治疗提供实验依据。
致敏小鼠在吸入OVA激发前3天，通过以下三种途径之一给予单剂量M. vaccae：肌肉注射（i.m.）、气管内滴注（i.t）或皮肤划痕接种（c.s）。测定BALF中炎症细胞的积聚情况、IFN-γ和IL-4水平。
M. vaccae 2.25μg（每只小鼠）c.s组BALF中炎症细胞总数为（6±6）×10⁸/L，2.25μg i.t组为（7±6）×10⁸/L，22.5μg i.m组为（8±5）×10⁸/L，均显著低于模型对照组（15±8）×10⁸/L（P<0.05）。2.25μg c.s组嗜酸性粒细胞数为0.7±0.5，2.25μg i.t组为1.6±1.9，7.5μg i.m组为2.6±1.3，22.5μg i.m组为1.40±1.20，均显著低于模型组4.90±4.60（P<0.05和P<0.01）。2.25μg c.s组IFN-γ水平为（289±57）pg/ml，2.25μg i.t组为（335±57）pg/ml，22.5μg i.m组为（313±49）pg/ml，均显著高于模型组（216±42）pg/ml（P<0.05和P<0.01）。2.25μg c.s组IL-4水平为（63±19）pg/ml，2.25μg i.t组为（8±5）pg/ml, 22.5μg i.m组为（13±6）pg/ml，均显著低于模型组（93±25）pg/ml（P<0.05和P<0.01）。气管内滴注或皮肤划痕接种M. vaccae对嗜酸性粒细胞积聚的抑制作用比肌肉注射M. vaccae强10倍。气管内滴注M. vaccae在调节IFN-γ/IL-4比值方面最有效。
M. vaccae通过调节Th1/Th2平衡抑制气道炎症，提示其可能对哮喘治疗有益。
