Modulation of Th1/Th2 cytokine production by selective and nonselective phosphodiesterase inhibitors administered to mice

Phosphodiesterase (pde) inhibitors can modulate the functions of immune cells,including t lymphocytes,due to increased intracellular levels of cyclic nucleotides. the drugs (aminophylline,milrinone and sildenafil) were administered once or five times at 24 h intervals at the following doses: 20 mg/kg,im,1 mg/kg,im and 1 mg/kg,po,respectively. th1 and th2 cytokine levels (il-2,ifn-γ,il-4,il-5,tnf) were determined 12,24 or 72 h after the last administration of the drugs. acommercial bd™ cytometric bead array mouse th1/th2 cytokine kit (cba) was used to determine the levels of th1/th2 cytokines in the serum. neither of the pde inhibitors under investigation administered once changed ifn-γ,tnf and il-4 production. asingle dose of aminophylline decreased the production of il-2 (after 12 h). a single dose of milrinone did not affect th1/th2 cytokine secretion. sildenafil administered once decreased the production of il-2 (after 72 h).atemporary enhancement in the level of il-5was observed 12 h after a single dose of sildenafil.no changes inth1 andth2 cytokine productionwere observed after five doses of pdeinhibitors under investigation. these results indicate that nonstimulated lymphocytes th1 and th2 exhibited a slight sensitivity to aminophylline and sildenafil. the drugs under investigation were ineffective inhibitors of th1/th2 cytokine production. copyright © 2012 by institute of pharmacology polish academy of sciences.