The influence of theophylline treatment on PGE2 production, PGE2 sensitivity and the distribution pattern of lymphocyte classes relative to the immune status.
In mice, theophylline reduced immune response mechanisms in case of primed cells but stimulated the reaction if priming and treatment were performed concomitantly. The reason for these bivalent reactions is unclear. We studied the effect of theophylline on prostaglandin E2 (PGE2) production by resident macrophages (M phi), on PGE2 sensitivity of thymocytes and spleen cells and on the distribution pattern of lymphocyte classes in thymus and spleen dependent on whether animals were immunized with sheep red blood cells (SRBC) or not. We found a theophylline induced decrease of PGE2 production of M phi in normal but an increase in immunized animals which was less pronounced if given concomitantly with a booster injection. The PGE2 resistance of thymocytes and spleen cells defined by the concentration of PGE2 needed for a 50% inhibition of PHA-P induced transformation was considerably increased by theophylline in normal animals. If given concomitantly with primary sensitization, theophylline equally increased PGE2 resistance but diminished it if applied together with a booster injection. This increase or decrease of PGE2 resistance ran parallel with a decrease or increase of the relative number of Lyt 2+ cells (suppressor T cells = Ts) in the thymus and in the spleen of theophylline treated animals. These results demonstrated that the bivalent effect of theophylline on immune response dependent on the immune status could predominantly be explained by its modulating effect on PGE2 sensitivity of thymocytes and spleen cells together with a corresponding shift in the number of Ts-cells, whereas the influence on PGE2 production by M phi seemed less important.
Gillissen
G
G
Breuer-Werle
M
M
Ostendorp
H
H
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D015232:Dinoprostone; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011458:Prostaglandins E / Q000096:biosynthesis* / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology*
D011458:Prostaglandins E; D013806:Theophylline; D015232:Dinoprostone