Effects of BCG on ovalbumin-induced bronchial hyperreactivity in a guinea pig asthma model

To test the effects of Bacillus Calmette-Guérin (BCG) on ovalbumin (OVA)-induced airway hyper-reactivity in guinea pigs, a total of 40 young guinea pigs was individually vaccinated subcutaneously with 0.2 mL of 2% OVA, 50 microg BCG, or a mixture of OVA and BCG (OVA+BCG). Airways were sensitized using nebulization with 1% OVA for 3 min once a week for two applications, followed by 2% OVA nebulized challenge for 3 min 1 week after the last application. Different concentrations of methacholine were used to detect airway hyperreactivities. At the third week, the guinea pigs were nebulized with either methacholine or OVA to test airway hyperreactivity. The OVA-vaccinated group presented with severe airway hyperresponsiveness after OVA and methacholine challenges; the BCG-vaccinated group showed mild airway hyperreactivity; and the OVA+BCG group showed the least amount of airway hyperreactivity. Lung histopathology in all groups, except the OVA+BCG-vaccinated group, showed severe thickening of the alveolar walls which became firmly fibrotic, and narrowing of the alveolar spaces was also noted. The guinea pigs in the OVA+BCG-vaccinated group had similar pulmonary morphology with that of naive guinea pigs, and had mild cell infiltration in the alveolar wall. The results of the skin biopsies at 6 h (2% OVA, 0.05 mL) and 36 h (20 microg PPD, 0.05 mL) after purified protein derivative (PPD) inoculation showed that infiltration of eosinophils and activation of CD4+ T-cells occurred in the OVA-vaccinated group. In the BCG-vaccinated groups, infiltration of CD4+ T-cells, CD8+ T-cells and macrophages occurred. OVA-specific IgG2 increased in the BCG-vaccinated groups after OVA-induced airway hyperreactivity occurred. The peripheral cell subpopulation showed that there was obviously increased activation of CD4+ and CD8+ T-cells in the OVA+BCG-vaccinated group. The phagocytic activity of macrophages also increased in both BCG- and OVA+BCG-vaccinated groups. The prevention of OVA-induced airway hyperreactivities using BCG vaccination in conjugation with OVA in these young guinea pigs indicated that it might be a good approach to avoid allergic reactions in humans.