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The in vitro incubation of phytohemagglutinin-stimulated peripheral blood lymphocytes with thymosin results in a marked and reproducible increase in production of T-cell growth factor, which is dose dependent and most pronounced in the first 24 hr of culture. Incubation of lymphocytes with thymosin alone failed to induce any production of Tcell growth factor. The biological activity of thymosin fraction 5 cannot be attributed to the activity of thymosin a,, one of the well-characterized peptide components of fraction 5. These data provide the basis for (i) a potential mechanism for the in vivo immunorestorative effects of thymosin in primary and secondary immunodeficiencies and (ii) identification of an additional, but as yet undefined, immunoregulatory component of thymosin fraction 5.The lymphokines are a group of mediators elaborated by activated lymphocytes that have important effects in the cascade of events following lymphocyte stimulation. T-cell growth factor (TCGF), also referred to as interleukin 2 (IL-2), has been widely studied (1) and is known to influence Tcell maturation, production of other lymphokines such as yinterferon (y-IFN) (2), and induction of natural killer and Tcell cytolytic activity (3,4). Recent attention has been focused both on the lack of TCGF production in certain immunodeficiency states and on the immunoregulatory potential of TCGF in enhancing depressed natural killer and virus specific cytotoxicity (5).The thymosins are a family of thymic humoral factors that have been proposed as hormonal agents with important immunoregulatory effects (6). Thymosins, as well as other thymic preparations, are being tested extensively in vivo, as biological response modifiers in clinical trials and experimental models of primary and secondary immunodeficiencies, including acquired immunodeficiency syndrome (AIDS), autoimmune disease, neoplasia, and aging (7-11). The (12)(13)(14). The biological properties of two of these peptides, thymosins a1 and f34, have been studied extensively (12, 13). It has been suggested from earlier studies that these two peptides do not account for all the biological activity of the parent compound (15-17).Since F5 increases immune responsiveness in children with primary immunodeficiencies (7) and in cancer patients (10), and is being tested in clinical trials of autoimmune disease (9) and the pre-AIDS complex (8), we asked whether F5 functions, at least in part, by modulating TCGF production. It has been reported that F5 and thymosin a1 increase production of migration inhibition factor (MIF) in the mouse and guinea pig (18, 19) and production of a-and y-IFN in mice (20) and humans (21). Thymulin (FTS, facteur thymique serique), another thymic factor, has been shown to increase TCGF production by cells of nude mice (22). Grinblat et al. have reported increased TCGF production by thymic humoral factor (THF) in aged animals (23).In this paper, we report that F5 substantially and consistently augments production of TCGF by peripheral blood lymphocytes (PBL) ...

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This report concerns the use of a minimum stress animal model for evaluating the neuromodulatory effects of interferon-alpha (IFN-alpha). Male Sprague-Dawley rats, 350-450 g, received jugular catheters and were habituated to handling and sampling arenas. These procedures will minimize stress usually associated with i.v. injections and blood sampling. Natural rat IFN-alpha/beta (RaIFN-alpha/beta) endotoxin free (Lee Biomolecular Research Laboratories, San Diego, CA) or recombinant human IFN-alpha, (rHuIFN-alpha) (a gift from Hoffman La Roche, Nutley, NJ) was injected into rats via catheter at various IFN concentrations. Controls were injected with either (1) vehicle (saline), (2) human or bovine serum albumin in saline, or (3) heat-denatured RaIFN-alpha/beta. Experiments were begun (0 h) at about 0900 h, and blood samples were withdrawn at intervals up to 2 h after IFN or control injections and replaced by the same volume of saline. The concentrations of corticosterone and ACTH in peripheral plasma were measured by radioimmunoassay. Both IFN, when injected at concentrations of 300 or 600 U/g body weight (U/gbw), stimulated an increase above 0 h levels of both hormones in the same animals. Additionally, the stimulation was also evident when compared with plasma hormone levels in animals injected with control substance in a parallel time course. After administration of 150 U/gbw of either IFN, only the increase in the blood corticosterone was significant. These studies demonstrate that both homospecific (RaIFN-alpha/beta) and heterospecific (rHuIFN-alpha) IFN preparations are capable of stimulating the pituitary-adrenal axis.

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