Modulation of endogenous prostaglandins by thymosin-alpha 1 in lymphocytes.

The effects of thymosin-alpha 1 on the stimulation of specific release of prostaglandin E2 (PGE2) from splenic lymphocytes and thymocytes were studied. Experiments were also performed to study in parallel the absolute levels of thymosin-alpha 1 in the blood and the induction of serum FTS activity and of azathioprine sensitivity of spleen cells from adult thymectomized (ATx) mice. A significant difference in the release of PGE2 between normal splenocytes and splenocytes from ATx mice was observed. Thymosin-alpha 1 at certain concentrations was able to stimulate PGE2 release from lymphocytes of ATx mice while inhibiting release in lymphocytes of normal mice. Also, thymocytes were stimulated to release PGE2 after incubation with alpha 1 in a manner similar to that seen in spleen cells of ATx mice. Approximately the same concentrations of alpha 1 was found to also correct the low azathioprine sensitivity of splenocytes from ATx mice. Determinations of FTS-like activity in the blood and the pharmacokinetics of alpha 1 after administration of this synthetic molecule show a clear dissociation. A maximum peak of alpha 1 activity was obtained after 1 hr, while maximal FTS-like activity was observed after 24 hr. The inhibition of the induction by alpha 1 of FTS-like activity and of Thy 1.2 antigen by indomethacin suggests that the action of alpha 1 requires prostaglandin biosynthesis.