Pentoxifylline and other methyl xanthines inhibit interleukin-2 receptor expression in human lymphocytes

Cell Immunol. 1991 Jul;135(2):314-25. doi: 10.1016/0008-8749(91)90276-h.


Addition of pentoxifylline to lymphocytes caused a dose-dependent decrease in PHA-induced interleukin-2 receptor (IL-2R) expression. Expression of IL-2R protein and mRNA were inhibited by 60% at a concentration of 1 mM. Pentoxifylline also inhibited release of IL-2R into the medium by 85%. Treatment with recombinant IL-2 (50 U/ml) did not abrogate the effect of pentoxifylline. In addition to inhibition of IL-2R expression, pentoxifylline also decreased the expression of transferrin receptors and class I MHC antigens. Pentoxifylline also inhibited cell proliferation. However, aphidicolin, an inhibitor of DNA polymerase alpha inhibited cell proliferation to the same extent as pentoxifylline, but had no effect on IL-2R expression, indicating that inhibition of cell proliferation does not necessarily lead to inhibition of IL-2R expression. The inhibitory effect on IL-2R expression was also noted with other methylxanthines, theophylline and isobutylmethylxanthine, and with dbcAMP and forskolin. The inhibitory activity of pentoxifylline was prevented by W-13, a calmodulin antagonist, but not by HA-1004, a cyclic AMP-dependent protein kinase inhibitor. This suggests that pentoxifylline might act in part through a Ca2+/calmodulin-dependent mechanism. Pentoxifylline and other methylxanthines may prove useful in delineating the biochemical pathways involved in induction and expression of cell surface receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Aphidicolin
  • Calmodulin / physiology
  • Cells, Cultured
  • Cyclic AMP / physiology
  • Diterpenes / pharmacology
  • Histocompatibility Antigens Class I / analysis
  • Humans
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocytes / drug effects*
  • Pentoxifylline / pharmacology*
  • RNA, Messenger / analysis
  • Receptors, Interleukin-2 / analysis*
  • Receptors, Interleukin-2 / drug effects
  • Receptors, Interleukin-2 / genetics
  • Receptors, Transferrin / analysis


  • Calmodulin
  • Diterpenes
  • Histocompatibility Antigens Class I
  • Interleukin-2
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Receptors, Transferrin
  • Aphidicolin
  • Cyclic AMP
  • Pentoxifylline
  • 1-Methyl-3-isobutylxanthine