EFFECTS OF IN-VIVO ADMINISTRATION OF ANTI-IL-10 MONOCLONAL-ANTIBODY ON THE HOST-DEFENSE MECHANISM AGAINST MURINE SALMONELLA INFECTION

Interleukin-10 (IL-10)is a cytokine that regulates various macrophage functions. To elucidate the involvement of endogenous IL-10 in the ear ly stage of murine salmonellosis, we examined the effect of anti-IL-10 monoclonal antibody (mAb) administration on the host defence mechanis m against Salmonella choleraesuis infection. The in vivo administratio n of anti-IL-10 mAb significantly enhanced host resistance at the earl y stage of Salmonella infection, as assessed by bacterial growth in th e peritoneal cavity and the liver. Enhanced levels of monokine mRNA, i ncluding IL-1 alpha, tumour necrosis factor-alpha (TNF-alpha) and IL-1 2, were observed from day 1 after infection in the peritoneal macropha ges in anti-IL-10 mAb-treated mice compared with those in control mAb- treated mice. Mice treated with anti-IL-10 mAb exhibited significantly higher levels of interferon-gamma (IFN-gamma) in the peritoneal exuda tes and major histocompatibility complex (MHC) class II expression on the peritoneal macrophages on days 3 and 5 after infection. Notably, i n vivo anti-IL-10 mAb brought about an increment of gamma delta T cell s in the peritoneal cavity at the early phase of infection, which was correlated with the expression of endogenous heat-shock protein 60 (HS P60), which is implicated as a potential ligand for gamma delta T cell s, in the infected macrophages. Our results suggest that the neutraliz ation of endogenous IL-10 accelerates some macrophage functions and, c onsequently, the activation of immunocompetent cells, including gamma delta T cells, at the early stage of infection, resulting in an enhanc ed host defence against Salmonella infection.