title: Does thalidomide affect IL-2 response and production?
abstract: 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.
authors.affiliation: Bone Marrow Transplantation Program, Stanford University Medical Center, CA 94305, USA.
authors.forename: L P
authors.initials: LP
authors.lastname: Fernandez
authors.forename: P G
authors.initials: PG
authors.lastname: Schlegel
authors.forename: J
authors.initials: J
authors.lastname: Baker
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: N J
authors.initials: NJ
authors.lastname: Chao
mesh_terms: D002478:Cells, Cultured; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D004742:Enhancer Elements, Genetic; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis / Q000096:biosynthesis*; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D007938:Leukemia; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013792:Thalidomide / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000032:analysis / Q000096:biosynthesis
chemical_list: D007376:Interleukin-2; D013792:Thalidomide; D015759:Ionomycin; D001616:beta-Galactosidase; D013755:Tetradecanoylphorbol Acetate