A molecule derived from mycobacterium tuberculosis Cpn60.1 (compound Y) inhibits lung inflammation induced by LPS in mice

Abstract

Introduction:We have previously shown that Cpn60.1 inhibits allergic pulmonary inflammation and bronchial hyperresponsiveness (BHR) in a murine model (Riffo-Vasquez, Y et al. AJRCMB,47(2):245, 2012). In this study we have investigated the effect of a shorter molecule derived from Cpn60.1 (compound Y) in a murine model of lung inflammation induced by LPS

Methods: Male BALB/c mice were pre-treated with compound Y (5-500 pg/mouse) intravenously minutes before intranasal instillation of LPS (25 µg). Controls received vehicle (saline) by the same route. Readouts were performed 4h later. Cytokines were measured in BAL using conventional ELISA, following instructions of the manufacturer. Results: Compound Y at 5, 50, but not 500 pg/mouse, significantly inhibited the number of neutrophils in the bronchoalveolar lavage (mean ± SEM x 10⁴/ml) (LPS: 212.8 ± 12.1 vs LPS/compound Y: 113.2 ± 22; 101.6 ± 14.4 and 194.5 ± 50 for 5, 50 and 500 pg/mouse, respectively. p<0.05, n=8/group). Compound Y at 5, 50, but not 500 pg/mouse, reduced levels of IL-12 (mean ± SEM pg/ml) (LPS: 698 ± 55 vs LPS/compound Y: 533 ± 52, 289 ± 48, 833.4 ± 200 for 0.5, 5 and 500 pg/mouse respectively, n=4/group) and IL-6 (LPS: 1034 ± 55 vs LPS/compound Y: 492 ± 86, 525 ± 73 and 1044 ± 263 for 0.5, 5 and 500 pg/mouse respectively, n=4/group). Conclusion: Compound Y significantly reduces cell migration and the release of pro-inflammatory cytokines induced by LPS in the lung.