IMMUNOTHERAPY WITH NATURAL INTERLEUKINS AND/OR THYMOSIN ALPHA(1) POTENTLY AUGMENTS T-LYMPHOCYTE RESPONSES OF HYDROCORTISONE-TREATED AGED MICE

Cytokines and thymic hormones are thought to play critical roles in the regulation of T-lymphocyte development and function. In an effort to determine the effectiveness of such agents in an immunotherapeutic strategy, we employed aged mice in a hydrocortisone treatment model to generate an immunodeficient state and to study its reconstitution. Mice were given five daily injections of a natural cytokine mixture (NCM), recombinant interleukins (rIL-1, rIL-2) or their combination, thymosin alpha(1) or fraction 5 (T alpha(1), TF5), or the combinations of NCM plus T alpha(1) and of NCM plus TF5. Spleen and thymus weights were obtained and the cellular responses to stimulation in vitro with NCM, IL-1, IL-2 and mitogens (PHA and Con A) were assayed. Both NCM and T alpha(1) in vivo treatment augmented thymocyte and splenocyte in vitro responses to both interleukins and mitogens. Neither treatments with equivalent doses of rIL-1, rIL-2 nor their combination, nor TF5 achieved similar results. Of all the treatments, only NCM plus T alpha(1) augmented spleen weight; none augmented thymus weight. Surface marker analyses of T-lymphocytes and subsets indicate that treatment of mice with NCM plus T alpha(1) increased spleen T-cell numbers of both CD4 and CD8 positive cells significantly. These data indicate that NCM and T alpha(1) alone and in combination may be therapeutically useful to restore T-lymphocyte number or function in secondary immunodeficiency.