The effects of 16,16-dimethyl PGE2 and phosphodiesterase inhibitors on Con A blastogenic responses and NK cytotoxic activity of mouse spleen cells.
Prostaglandins function as down regulators of immune responses probably by increasing the concentration of intracellular cAMP. Phosphodiesterase inhibitors, which prevent the breakdown of cAMP, also increase the intracellular levels of cAMP. Prostaglandins and phosphodiesterase inhibitors have both been shown to suppress immune responses in vitro. In this study 16,16-dimethyl PGE2 (dm-PGE2), added in vitro, suppressed the mouse spleen cell concanavalin A (Con A) response by 38% and natural killer (NK) activity by 53%. Addition of the phosphodiesterase inhibitors, theophylline, RO20-1724, or dipyridamole, decreased both the Con A response and NK activity by at least an additional 30%. We also demonstrate that treatment with dm-PGE2 and theophylline in vivo is more effective than either compound alone in inhibiting NK activity of both untreated mice and mice treated with polyinosinic-polycytidylic acid. These studies support the hypothesis that the immunosuppressive effect of dm-PGE2 is mediated by cAMP and suggest that treatment with a combination of dm-PGE2 and phosphodiesterase inhibitors can augment this immunosuppressive effect.
Ellis
N K
NK
Department of Laboratory Service, Edward J. Hines, Jr., Veterans Administration Hospital, Hines, IL 60141.
Duffie
G P
GP
Young
M R
MR
Wepsic
H T
HT
D015064:16,16-Dimethylprostaglandin E2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000502:physiology; D004176:Dipyridamole / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D013806:Theophylline / Q000494:pharmacology
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011459:Prostaglandins E, Synthetic; D003208:Concanavalin A; C048819:4-(3,4-dibutoxybenzyl)-2-imidazolidinone; C054703:16,16-dimethylprostaglandin E2 (4-acetamidobenzamido)phenyl ester; D004176:Dipyridamole; D013806:Theophylline; D000242:Cyclic AMP; D015064:16,16-Dimethylprostaglandin E2