Interferon-α receptor expression and regulation in chronic hepatitis B virus infection

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Abstract

Interferon-α elicits antiviral and immunoregulatory activities by binding to specific receptors on the cell surface. In this study, binding characteristics of interferon-α to peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection were studied using radioiodinated recombinant interferon-α2b to determine interferon-α receptor numbers and dissociation constants. A single class of interferon-α receptor was demonstrated on peripheral blood mononuclear cells and mononuclear subsets. Peripheral blood mononuclear cells from patients with chronic hepatitis B virus infection (n = 20) and controls (n = 16) expressed a similar number of interferon-α receptors (484 ± 175 vs. 511 ± 168 sites/cell respectively, p = NS) with a similar dissociation constant (dissociation constant ± 0.2 to 0.7 nmol/L). Expression of interferon-α receptors was similar in monocyteenriched and lymphocyte-enriched fractions in both groups. Similar changes were observed in patients receiving α-interferon therapy. There was no correlation between interferon-α receptors expression and serum transaminase, serum HBsAg, serum HBV DNA, liver histological findings or the response to interferon-α therapy.

After incubation of lymphocytes in vitro with interferon-α2b (10 to 1,000 U/ml), interferon-α receptors number dropped by 42% to 80%, but this was associated with an increase in binding affinity (dissociation constant ≈ 0.05 to 0.15 nmol/L) in both patients and controls. There was significant delay in the initial phase of receptor recovery in the patients with chronic hepatitis B virus infection compared with normal controls (days 1 and 2, p <0.05).

These data indicate that interferon-α receptors are expressed and regulated normally in chronic hepatitis B virus infection and that the variable response to interferon-α therapy is not due to a variation in interferon-α receptor. The increase in binding affinity on interferon-α therapy may be one factor explaining why long-term interferon-α therapy is effective despite a decrease in receptor number. (HEPATOLOGY 1991;13:332–338).

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