Decreased in vitro Production of Tumor Necrosis Factor in Primary Biliary Cirrhosis Patients

Abstract

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are characterized by immunoregulatory disturbances and fibrosis. Several cytokines may be of importance for the inflammatory response and the development of fibrosis. In the present study the capacity to produce tumor necrosis factor (TNF) and interleukin-1 (IL-1) was determined in 11 patients with PSC, 10 patients with PBC, and 20 healthy control subjects. As compared with the controls, in vitro cultured mononuclear cells from PBC patients showed a lower spontaneous TNF production (median, 16,499 cpm; range, 7181–41,907; p < 0.02), whereas the TNF production of PSC patients was similar to that of the controls. Lipopolysaccharide (LPS)-stimulated TNF production was also lower in the PBC group (median, 40,564 cpm; range, 23,493–69,452) than in PSC patients (median, 58,898 cpm; range, 37,997–91,485; p < 0.03). The spontaneous and LPS-stimulated IL-1 production did not differ in patients and healthy controls. The cytokine production in patients with PBC and PSC did not correlate to histologic activity, associated diseases such as ulcerative colitis and bilirubin, or to Child-Pugh classification. Thus, in contrast to hepatocellular diseases, in which cytokine production is reported to be increased, PBC and PSC are accompanied by low or normal TNF and IL-1 production.

Key Words:

• Cholestatic liver disease
• cytokines
• interleukin-1
• tumor necrosis factor