THYMULIN MODULATES CYTOKINE RELEASE BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS - A COMPARISON BETWEEN HEALTHY-VOLUNTEERS AND PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

Thymulin is a nonapeptide hormone isolated from the thymus gland. It h as immunomodulatory effects which have not yet been well defined. Its major actions have been shown to be on T-cells and their immature prec ursors. In this study, thymulin was tested in vitro for its effect on the release of IL-1alpha, IL,2, IL-6 and TNFalpha from peripheral bloo d mononuclear cells (PBMC) obtained from normal volunteers and patient s with active systemic lupus erythematosus (SLE). In our experiments, PBMC (stimulated with LPS or PHA) were cultured for 24 h in the presen ce of 1, 100 or 1,000 ng/ml of thymulin. Supernatants were subsequentl y assayed for cytokine activities using commercially available ELISA ( IL-2, IL-6 and TNFalpha) and RIA (IL-1alpha) kits. Thymulin (1 ng/ml) resulted in a significant (p < 0.01) increase in IL-1alpha in the volu nteers and a significant (p < 0.05) inhibition of this cytokine at all dose levels tested in SLE patients, whose basal levels of IL-1alpha w ere significantly (p < 0.05) higher. Thymulin significantly (p < 0.05) inhibited IL-2 only in SLE patients at 1,000 ng/ml. At ail dose level s tested, thymulin significantly (p < 0.01) inhibited IL-6 in voluntee rs, and, only at 1,000 ng/ml, it significantly (p < 0.05) inhibited it in patients with SLE. At the 1,000 ng/ml dose level, TNFalpha was sig nificantly (p < 0.05) inhibited in both volunteers and SLE patients, w hose basal levels of this cytokine were significantly (p < 0.05) highe r. Our results indicate that thymulin may function as an immunomodulat or by exerting control on cytokine production by PBMC.