An interleukin-1 receptor antagonist decreases fibrosis induced by dimethylnitrosamine in rat liver.
The main pathological feature of liver fibrosis is the accumulation of extracellular matrix associated with hyperplasia and activation of perisinusoidal (Ito) cells (PSC) to myofibroblast-like cells. Interleukin-1 enhances collagen synthesis by increasing the proliferative activity of cultured PSC and has been implicated in the pathogenesis of hepatic fibrosis. Interleukin-1 receptor antagonist (IL-1ra) can block the binding of IL-1 to its receptors and act as a natural inhibitor of IL-1. We have examined whether the administration of IL-1ra can interfere with the development of experimental cirrhosis induced by dimethylnitrosamine (DMN). Rats were divided in three groups and received respectively DMN, DMN + IL-1ra and IL-1ra. For each group the collagen content of the hepatic tissue and the volume density of the inflammatory infiltrate were measured. Immunostaining for laminin and alpha-smooth muscle actin were also performed. In animals given DMN + IL-1ra we observed a decreased deposition of laminin and collagen, and a decreased number of laminin-positive PSC and of alpha-smooth muscle actin reactive cells, compared with animals receiving DMN alone. The present findings suggest that the early activation of PSC in vivo is at least in part mediated by IL-1 and confirm that the administration of IL-1ra may be of interest in modifying the biological effects of IL-1.
Mancini
R
R
Department of Gastroenterology, University of Ancona, Italy.
Benedetti
A
A
Jezequel
A M
AM
D000199:Actins / Q000032:analysis; D000818:Animals; D003094:Collagen / Q000032:analysis; D004128:Dimethylnitrosamine; D007124:Immunoenzyme Techniques; D007797:Laminin / Q000032:analysis; D008099:Liver / Q000098:blood supply / Q000737:chemistry / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009130:Muscle, Smooth / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*
D000199:Actins; D007797:Laminin; D017472:Receptors, Interleukin-1; D003094:Collagen; D004128:Dimethylnitrosamine