Effect of interferon-γ on hepatitis B viral antigen expression in primary hepatocyte culture

✍ Scribed by Dr. Johnson Y. N. Lau; Vincent G. Bain; Nikolai V. Naoumov; Heather M. Smith; Graeme J. M. Alexander; Roger Williams

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 542 KB
• Volume: 14
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840140604

✦ Synopsis

Interferon-a has been shown recently to selectively enhance hepatocyte expression of HBsAdpre-S, in chronic hepatitis B virus infection in a way that may enhance immune recognition. To determine the effect of interferon? on hepatitis B virus antigen expression, hepatocytes isolated from patients with chronic hepatitis B virus infection were incubated in the absence or presence of interferon? and viral antigen expression was assessed by both radiohunoassay and immunocytochemistry using appropriate monoclonal antibodies.

Interferon? inhibited the expression of aII hepatitis B virus antigens tested. Intracellular HBsAg measured by radioimutunoassay of sonicated hepatocytes fell by 29% with 1 U/ml (p < 0.01) and 36% with 10 U/ml of interferon? (p < 0.001) compared with control treatment. Secreted HBsAg was reduced by 19% with 10 U/ml of interferon-y (p < 0.01). Intracellular HBeAg was also decreased by 29% with 1 U/ml (p < 0.05) and 42% with 10 U/ml of interferon-y (p < 0.051, but no significant change was found in the amount of secreted

HBeAg. The proportion of hepatocytes containing

various hepatitis B virus antigens and the intracellular viral antigen staining densities also fell significantly with interferon-y incubation. Interestingly, the addition of interferon-y abolished the augmenting effect of interferon-a on intracellular HBsAg. These data indicate that interferon-y, in contrast to interferon-a, has an inhibitory effect on hepatocyte expression of all hepatitis B virus antigens including HBsAg/pre-S,, suggesting that this may be one factor that accounts for their difference in clinical activity in patients with chronic hepatitis B virus infection.

(HEPATOLUGY 1991;14:975-979.)

Of all the agents that have been used to treat chronic HBV infection, interferon-a (IFNa) has been the most promising, although its mode of action in clearing HBV