Thymosin-alpha 1 increases the capability to produce interleukin-3 but not interleukin-2 in nu/nu mice.

Thymosin-alpha 1 increased the capability of nu/nu mice to produce interleukin (IL)-3 but not IL-2 when administered intraperitoneally at doses of 0.5 and 5.0 micrograms/kg twice a week for 3-6 weeks. Thy-1-positive cells were responsible for the production of IL-3, which was determined by proliferation of the IL-3-dependent cell line (FDC-P2) as well as by augmentation of the in vitro growth of hematopoietic stem cells (colony-forming unit S [CFU-S]). The IL-3 activity released by nu/nu splenocytes emerged in fractions coincidentally with IL-3 released by WEHI-3 cells on Mono Q anion-exchange chromatography. However, IL-2 activity determined by proliferation of the IL-2-dependent cell line was not detected in any fractions of the same chromatography. These findings indicate that IL-2 is not always coproduced with IL-3 by Thy-1-positive cells. This suggests, taken together with results from previous studies about the cells producing IL-2 and IL-3 by other investigators, that thymosin-alpha 1 exerts its effect at an early stage of T cell differentiation to induce a T cell subpopulation capable of producing IL-3 (but not yet IL-2). Based on the present findings, we discuss the mechanism of action by which thymosin-alpha 1 exerts its diverse effects in immunosuppressed hosts but not a potentiating effect in healthy normal animals or in in vitro assays of T cell function.