Preparation of specific antibodies against murine IL-1ra and the establishment of IL-1ra as an endogenous regulator of bacteria-induced fulminant hepatitis in mice.
Blocking monoclonal antibodies (mAbs) specific to mouse interleukin-1 receptor antagonist (IL-1ra) were prepared by immunizing Armenian hamsters with recombinant mouse IL-1ra. A sensitive and specific ELISA against mouse IL-1ra was also established. In Propionibacterium acnes-induced liver injury, P. acnes induced transient increase of serum tumor necrosis factor-alpha levels but not those of IL-1ra, IL-1, and IL-6. However, subsequent lipopolysaccharide (LPS) challenge induced the increase of serum levels of all these cytokines and the peak serum IL-1ra level was more than 20 times as high as serum IL-1 levels. Immunohistochemical analysis demonstrated that IL-1ra was predominantly produced by hepatocytes during the course of the priming phase by P. acnes and eliciting phase by LPS challenge. Furthermore, the administration of a mAb to mouse IL-1ra exacerbates the liver injury induced by P. acnes and sublethal dose of LPS, suggesting a protective role of endogenous IL-1ra in this liver injury model.
Fujioka
N
N
Department of Surgery, Cancer Research Institute, Ishikawa, Japan.
Mukaida
N
N
Harada
A
A
Akiyama
M
M
Kasahara
T
T
Kuno
K
K
Ooi
A
A
Mai
M
M
Matsushima
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000502:physiology*; D004195:Disease Models, Animal; D006505:Hepatitis / Q000473:pathology / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D011425:Propionibacterium acnes / Q000472:pathogenicity; D011817:Rabbits; D012795:Sialoglycoproteins / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016207:Cytokines; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha