Inhibition of the acute-phase response in vivo by anti-gp130 monoclonal antibodies.
The acute-phase response is believed to be an important systemic defence reaction to inflammation during infection, trauma, injury or neoplasia. Although the interleukin-6 (IL-6) family of cytokines appear to be the major regulators of the acute-phase reaction, the exact biological significance of this process remains unknown. In this study, a panel of monoclonal antibodies (Mabs) was raised against the extracellular domain of human gp130 (the common signal transducing chain of the IL-6 cytokine family) in order to inhibit the biological activity of IL-6-like cytokines in vivo. Mabs designated 4B11 and 2H4 were most effective in the inhibition of the in vitro acute-phase response on hepatoma cells and prevented the IL-6-induced growth inhibition of A375 cells. Administration of the antibodies to dogs at a dosage of 8 mg/kg/d showed that 2H4 was a potent inhibitor of the IL-6-induced (40 micrograms/kg/d) acute-phase response, abrogating IL-6-mediated increments in fibrinogen, C-reactive protein and the platelet count. This antibody, the first described to abrogate the acute-phase response in vivo, may not only permit development of a new anti-inflammatory strategy, but provides an excellent tool for defining the function of acute-phase proteins in inflammation and infection.
Harrison
P
P
Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City 73190, USA.
Downs
T
T
Friese
P
P
Wolf
R
R
George
J N
JN
Burstein
S A
SA
D000210:Acute-Phase Reaction / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000378:metabolism; D006825:Hybridomas / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D017370:Interleukin-11 / Q000037:antagonists & inhibitors; D008546:Melanoma, Experimental / Q000276:immunology; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism; D010976:Platelet Count; D014407:Tumor Cells, Cultured; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D002097:C-Reactive Protein; D005340:Fibrinogen; D017370:Interleukin-11; D053683:Oncostatin M; D010455:Peptides; D000093242:Interleukin-6 Inhibitors; C508351:OSM protein, human