Peritoneal lavage fluids stimulate NIH3T3 fibroblast proliferation and contain increased tumour necrosis factor and IL-6 in experimental silica-induced rat peritonitis

Abstract

Fibroblast proliferation is one of the earliest features of fibrosis, preceding collagen deposition in wound. The response to tissue injury is characterized by the infiltration of acute inflammatory cells, followed by persistence of macrophages. In vitro, macrophages are known to secrete monokines and growth factors which affect fibroblast proliferation and collagen synthesis. To investigate in vivo kinetics of fibroblast proliferating activity and monokine production in experimental peritonitis, silica was instilled intraperitoneally into rats, and peritoneal lavage fluids (PLF) and the culture supernatants of macrophages were analysed for NIH3T3 fibroblast proliferating activity and monokine production. NIH3T3 fibroblast proliferating activity in PLF was markedly elevated 3-5 days after intraperitoneal silica instillation, and peritoneal macrophages also spontaneously released these factors in vitro. Tumour necrosis factor (TNF) and IL-6 were also markedly increased after 3-5 days, and macrophages spontaneously released these monokines. PLF-induced fibroblast proliferation was blocked by anti-TNF antibody, and fibroblast proliferation was stimulated by the external addition of TNF or TNF and IL-6 in vitro. These results show high influx of fibroblast proliferating factors and monokines in peritoneal lavage fluid after 3-5 days of silica-induced experimental peritonitis, providing further evidence of involvement of macrophages, TNF, and possibly IL-6 in peritoneal fibrosis.