Lymphocyte suppression by rolipram with other immunosuppressive drugs.
Pentoxifylline, a nonselective phosphodiesterase inhibitor, has immunomodulatory activity in vitro and in vivo and potentiates the suppressive effects of glucocorticoids and cyclosporine on lymphocyte proliferation in vitro. Since phosphodiesterase isotypes 3 and 4 predominate in lymphocytes, the authors measured the suppressive effect of rolipram alone and in combination with low concentrations of methylprednisolone and calcineurin enzyme inhibitors, compared to that of pentoxifylline on mitogen-stimulated lymphocyte proliferation. The percent inhibition of 3H-thymidine incorporation by both 10(-5) and 10(-8) mol/L concentrations of rolipram were significantly greater than that by both 10(-4) mol/L pentoxifylline and 10(-8) mol/L methylprednisolone. The percent inhibition by the combination of 10(-5), but not 10(-6), mol/L rolipram and methylprednisolone was significantly greater than that by 10(-4) mol/L pentoxifylline and methylprednisolone. Potentiation of the suppressive effects of cyclosporine and tacrolimus by rolipram was less consistent. Measurement of cell culture supernatant concentrations of interferon gamma and interleukin-10 indicate that one of the mechanisms underlying the immunosuppressive activity of rolipram is a significantly disproportionate inhibition of the proinflammatory cytokine, interferon gamma.
Briggs
W A
WA
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Wu
Q
Q
Orgul
O
O
Choi
M
M
Scheel
P J
PJ
Burdick
J
J
D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D015331:Cohort Studies; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D016753:Interleukin-10 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D020889:Rolipram; D016559:Tacrolimus / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D007166:Immunosuppressive Agents; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D014316:Tritium; D016753:Interleukin-10; D007371:Interferon-gamma; D016572:Cyclosporine; D020889:Rolipram; D010431:Pentoxifylline; D013936:Thymidine; D016559:Tacrolimus; D008775:Methylprednisolone