02965nas a2200385   4500000000100000008004100001260001300042653002300055653002000078653001600098653003700114653003100151653003800182653001100220653001800231653001400249653001300263653001300276653002600289653001600315653003300331653001600364653001700380653002600397100001800423700001700441700001200458700001100470700001300481245005800494300001100552490000700563520199500570022001402565       1995                            d  c1995 Aug10aBeta-Galactosidase10aCells, Cultured10aClone Cells10aDose-Response Relationship, Drug10aEnhancer Elements, Genetic10aEnzyme-Linked Immunosorbent Assay10aHumans10aInterleukin-210aIonomycin10aKinetics10aLeukemia10aLymphocyte Activation10aLymphocytes10aTetradecanoylphorbol Acetate10aThalidomide10aTransfection10aTumor Cells, Cultured1 aFernandez L P1 aSchlegel P G1 aBaker J1 aChen Y1 aChao N J00aDoes thalidomide affect IL-2 response and production?  a978-850 v233 a<p>The exact mechanism of immunosuppression by thalidomide is poorly understood. A common denominator in the pathogenesis of graft-vs.-host disease, graft rejection, reactional lepromatous leprosy, and autoimmune disorders modulated by thalidomide is the activation of T lymphocytes culminating in the synthesis of interleukin-2 (IL-2), the expression of high-affinity IL-2 receptors, and the induction of proliferation. We investigated the effect of thalidomide on the production of IL-2 by the human leukemia cell line Jurkat through induction of IL-2 gene enhancer activity and through the presence of IL-2 in supernatants. beta-galactosidase activity, encoded by a reporter lac z construct and controlled by a transcription factor in thalidomide-treated PMA- and ionomycin-stimulated Jurkat cells, was similar (97 +/- 1.33%; p > 0.1) to non-thalidomide-treated controls at all drug concentrations tested. IL-2 enhancer-driven beta-galactose activity of thalidomide-treated and stimulated cells was also similar to that of untreated controls (p > 0.2). The IL-2 production of activated nontransfected Jurkat cells was gauged by using the IL-2-dependent cell line HT-2 as a readout and by ELISA. Jurkat cells were subcloned by limiting dilution. Bulk cultures and three subclones (J.5.2.5., J.5.2.9., and J.5.3.8.) were assayed at 6, 12, and 24 hours after PHA/PMA-induced stimulation. No inhibitory effect on the IL-2 production by thalidomide could be detected at any of the drug concentrations tested (5-30 micrograms/mL), whereas 10 to 100 ng/mL of cyclosporine inhibited the IL-2 production by 95 to 100%. In addition, we observed neither inhibition of IL-2-dependent proliferation of HT-2 nor inhibition of PHA-induced proliferation of peripheral mononuclear cells by thalidomide at all drug concentrations used (5-30 micrograms/mL). These results do not support the possibility of a modulatory effect on the immune response by thalidomide via IL-2 production and IL-2 response.</p>  a0301-472X