Premium
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
Author(s) -
Fujioka Nakaba,
Mukaida Naofumi,
Harada Akihisa,
Akiyama Mariko,
Kasahara Tadashi,
Kuno Kouji,
Ooi Akishi,
Mai Masayoshi,
Matsushima Kouji
Publication year - 1995
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.58.1.90
Subject(s) - propionibacterium acnes , biology , interleukin 1 receptor antagonist , lipopolysaccharide , interleukin , immunology , antibody , tumor necrosis factor alpha , monoclonal antibody , fulminant hepatitis , endogeny , fulminant , receptor antagonist , cytokine , receptor , hepatitis , endocrinology , antagonist , bacteria , biochemistry , genetics
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 αcnes‐induced liver injury, P. acnes induced transient increase of serum tumor necrosis factor‐α 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. J. Leukoc. Biol. 58: 90–98; 1995.