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, i.m., 1 mg/kg, i.m. and 1 mg/kg, p.o., 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. A commercial 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. A single 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). A temporary enhancement in the level of IL-5 was observed 12 h after a single dose of sildenafil. No changes in Th1 and Th2 cytokine production were observed after five doses of PDE inhibitors 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.