title: Modulating effects of nonselective and selective phosphodiesterase inhibitors on lymphocyte subsets and humoral immune response in mice.
abstract: Phosphodiesterase (PDE) inhibitors can regulate the activity of immune cells by increasing intracellular levels of cyclic nucleotides. The aim of this study was to determine the effects of milrinone, a selective PDE3 inhibitor, sildenafil, a selective PDE5 inhibitor, and aminophylline, a nonselective PDE inhibitor, on lymphocyte subsets and humoral immune response in mice when administered in vivo. Aminophylline (20 mg/kg, i.m.), milrinone (1 mg/kg, i.m.) or sildenafil (1 mg/kg, p.o.) were administered to mice either once or five times at 24 h intervals. Some mice were immunized with a sheep red blood cell (SRBC) suspension administered i.p. either 2 h after the single dose or 2 h after the second of the five doses. In non-immunized mice treated five times with PDE inhibitors, the subsets of T lymphocytes in the thymus and T and B lymphocytes in the spleen and mesenteric lymph nodes were determined 12, 24 or 72 h after the last dose. The humoral immune response was determined on days 4, 7 and 14 after SRBC injection in SRBC-immunized mice treated with PDE inhibitors. A modulating effect of the drugs on lymphocyte subpopulations was observed. The greatest impact was observed in splenocyte subpopulations, and resulted in decreased percentages of B cells (CD19(+)) and increased percentages of T cells (CD3(+), CD4(+), CD8(+)). No effect or slight influence of the drugs on anti-SRBC hemagglutinins was observed, but the number of plaque-forming splenocytes was increased. The drugs under investigation did not show a significant immunosuppressive effect.
authors.affiliation: Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Norwida 31, PL 50-375 Wrocław, Poland. marianna.szczypka@up.wroc.pl
authors.forename: Marianna
authors.initials: M
authors.lastname: Szczypka
authors.forename: Bożena
authors.initials: B
authors.lastname: Obmińska-Mrukowicz
mesh_terms: D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D056724:Immunity, Humoral / Q000187:drug effects*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020105:Milrinone / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology; D011687:Purines / Q000378:metabolism / Q000494:pharmacology; D012756:Sheep / Q000276:immunology; D000068677:Sildenafil Citrate; D013154:Spleen / Q000166:cytology; D013450:Sulfones / Q000378:metabolism / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000628:Aminophylline; D000068677:Sildenafil Citrate; D020105:Milrinone