Effect of thymosin immunostimulation with and without corticosteroid immunosuppression on chimpanzee hepatitis B carriers

Abstract

Carriers of hepatitis B surface antigen (HBsAg) are at a high personal risk of developing chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma, and they pose a potential health threat to others. Accordingly, erradication of the carrier state is an important therapeutic goal. Several categories of drugs have been evaluated for this purpose, with, at best, limited success. The immune stimulants constitute a drug group considered to have potential benefit, since altered cell-mediated immunity (CMI) appears to have a pathogenic role in the perpetuation of the carrier state. One such immune stimulant is the thymic hormone, thymosin, which is known to enhance suppressor T-cell activity. We therefore examined its possible therapeutic role by evaluating its effect on four chronic HBsAg- and hepatitis B e antigen (HBeAg)-positive chimpanzees. After baseline biochemical, serological, immunological, and histochemical studies were conducted, all four chimpanzees received parenteral thymosin for a period of 10–14 weeks; two of them were pretreated for 4 weeks with corticosteroids. All four were then reevaluated in the same manner at regular intervals during the 14-week period. Neither immunosuppression nor immunostimulation significantly affected biochemical, serological, or histological measures. Indices of CMI were altered, however: both T4 and T8 cells increased with thymosin treatment, although the T4/T8 ratio declined because of the relatively greater increase of the T8 than of the T4 cells. Thymosin did not affect the mitogen assays. Thus, while immunostimulation with thymosin did slightly alter CMI, it had no affect on the HBsAg carrier state or on measures of chronic hepatitis, even when preceded by corticosteroid immunosuppression.