@article{17463,
  keywords = {Beta-Galactosidase, Cells, Cultured, Clone Cells, Dose-Response Relationship, Drug, Enhancer Elements, Genetic, Enzyme-Linked Immunosorbent Assay, Humans, Interleukin-2, Ionomycin, Kinetics, Leukemia, Lymphocyte Activation, Lymphocytes, Tetradecanoylphorbol Acetate, Thalidomide, Transfection, Tumor Cells, Cultured},
  author = {Fernandez L P and Schlegel P G and Baker J and Chen Y and Chao N J},
  title = {Does thalidomide affect IL-2 response and production?},
  abstract = {<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>},
  year = {1995},
  journal = {Experimental hematology},
  volume = {23},
  pages = {978-85},
  month = {1995 Aug},
  issn = {0301-472X},
  language = {eng},
}