Effects of in vivo administration of anti-IL-10 monoclonal antibody on the host defence 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 early stage of murine salmonellosis, we examined the effect of anti-IL-10 monoclonal antibody (mAb) administration on the host defence mechanism against Salmonella choleraesuis infection. The in vivo administration of anti-IL-10 mAb significantly enhanced host resistance at the early stage of Salmonella infection, as assessed by bacterial growth in the peritoneal cavity and the liver. Enhanced levels of monokine mRNA, including IL-1 alpha, tumour necrosis factor-alpha (TNF-alpha) and IL-12, were observed from day 1 after infection in the peritoneal macrophages 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 exudates and major histocompatibility complex (MHC) class II expression on the peritoneal macrophages on days 3 and 5 after infection. Notably, in vivo anti-IL-10 mAb brought about an increment of gamma delta T cells in the peritoneal cavity at the early phase of infection, which was correlated with the expression of endogenous heat-shock protein 60 (HSP60), which is implicated as a potential ligand for gamma delta T cells, in the infected macrophages. Our results suggest that the neutralization of endogenous IL-10 accelerates some macrophage functions and, consequently, the activation of immunocompetent cells, including gamma delta T cells, at the early stage of infection, resulting in an enhanced host defence against Salmonella infection.
Arai
T
T
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya, Japan.
Hiromatsu
K
K
Nishimura
H
H
Kimura
Y
Y
Kobayashi
N
N
Ishida
H
H
Nimura
Y
Y
Yoshikai
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D015153:Blotting, Western; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D016753:Interleukin-10 / Q000276:immunology*; D007700:Kinetics; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015846:Monokines / Q000096:biosynthesis; D010529:Peritoneal Cavity / Q000382:microbiology; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D012475:Salmonella / Q000254:growth & development; D012481:Salmonella Infections, Animal / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006360:Heat-Shock Proteins; D015846:Monokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016753:Interleukin-10