Thymosin Treatment Modulates Production of Interferon

Abstract

The maturation of T lymphocytes, the major producers of gamma interferon (IFN- γ), is regulated by thymic hormones. These studies were undertaken to determine whether or not thymic hormones also regulate the production of interferons by C57B1/6 mice. The results clearly indicate an important interrelationship between thymosin and production of interferon. Subcutaneous injection of a single dose of 100 μg or 200 μg of thymosin fraction 5 approximately 40 hr before induction of interferon with Newcastle disease virus (NDV) significantly augmented serum interferon titers compared to the interferon titers induced in untreated mice. Maximum enhancement was observed when a single injection of thymosin fraction 5 was administered between 6 and 12 hr before NDV. Two purified thymosin polypeptides,α₁ which induces maturation of helper T cells and α₇ which induces maturation of suppressor T cells, had opposite effects. Three injections of 5 μg of thymosin α₁ administered before NDV increased production of interferon while 3 daily injections of 1 μg of thymosin α₇, suppressed the responsiveness of mice to NDV. This observation represents the first report of a direct effect of purified thymic hormones on the production of interferon. Thymosin fraction 5 also enhanced production of IFN- γ. Enhanced interferon production was observed in Concanavalin A (Con A)-stimulated cultures of spleen cells from mice treated in vivo with 150 pg of thymosin fraction 5. The circadian rhythm of thymosin α₁ levels and the titer of interferon induced conincided. Significantly higher titers of interferon were induced when NDV was injected at midnight than were induced when NDV was injected in the morning. The results of this study suggest a significant role for the endocrine thymus in modulating interferon production and provide a rationale for exploring the role of thymosin in the treatment of viral diseases and perhaps other infectious diseases.