Interleukin-1 and interleukin-2 activity in chronic hepatitis B virus infection

Abnormalities of lymphocyte proliferation in chronic hepatitis B virus infection are well documented, although the underlying mechanisms are poorly understood. To determine whether these defects may be secondary to disordered lymphokine production, we have simultaneously assayed interleukin-1 and interleukin-2 production in 31 chronic carriers of the hepatitis B virus. Supernatants from mononuclear cells cultured both in the presence and absence of lipopolysaccharide contained significantly increased quantities of interleukin-1 activity in patients compared with normal controls (p less than 0.01). Lysates of monocytes from patients also contained more interleukin-1 than those of controls (p less than 0.05) in the presence of lipopolysaccharide or silica, or both. These results indicate that interleukin-1 production is markedly elevated in patients with chronic hepatitis B virus infection, whereas in contrast, interleukin-2 production was found to be reduced in these patients (p less than 0.01). As one of the biological properties of interleukin-1 is to stimulate fibroblasts to produce collagen, the relationship between fibrosis in the liver biopsy specimen and interleukin production was examined. There was a highly significant correlation (p less than 0.001) between interleukin-1 production and the severity of fibrosis, suggesting that this lymphokine may be closely related to the development of cirrhosis in such patients.