Fibroblast Proliferating Activity of Peripheral Mononuclear Cells in Hepatic Fibrosis

In order to clarify the immunological mechanism of hepatic fibrosis, peripheral mononuclear cells (PMNC) from patients with chronic hepatitis and liver cirrhosis were examined to know whether they release some fibroblast proliferating factors in response to PHA stimulation or not. The results obtained were as follows: 1) In the culture medium of PHA stimulated PMNC from patients with chronic hepatitis and liver cirrhosis, significantly higher activities of fibroblast proliferation were demonstrated as compared to those from normal subjects. 2) The cultured medium obtained from CAH was fractionated on high performance liquid chromatography and the activities were recovered in two peaks with a molecular weight of 60,000 (FPF-I) and 20,000 daltons (FPF-II), respectively. Both active peaks coincide with those of collagen synthesis. 3) The flat bed isoelectric focusing study of FPF-I and FPF-II revealed that p. I. of both fractions existed at 5. 1. 4) FPF-I and II coincide with active peaks of interleukin 1 (IL-1) activity as assessed by thymocyte proliferating assay and CTLL proliferating assay. 5) The macrophage fractions of PMNC from patients with chronic hepatitis and liver cirrhosis were found to secrete a fibroblast proliferating factor in relatively higher concentrations by the stimulation of LPS. It was assumed from the above results that the macrophage population in PMNC of chronic hepatitis or liver cirrhosis produces more IL-1 than normal subjects and thus the secreted IL-1 caused proliferation of fibroblast in the liver