Theophylline Inhibits the Production of Nitric Oxide by Peripheral Blood Mononuclear Cells from Patients with Asthma

Nitric oxide (NO), a reactive free radical synthesized from L-arginine by the enzyme NO synthase (NOS), may play a role in many pathophysiologic conditions, including asthma. The aim of this study was to investigate whether peripheral blood mononuclear cells (PBMCs) from asthmatics would spontaneously produce NO. A second objective was to ascertain whether commonly used asthma medications would modulate the production of NO. PBMCs were isolated from 24 subjects (10 with asthma, 4 with allergic rhinitis, and 10 healthy controls) and were incubated either alone or in the presence of an RNA polymerase inhibitor (actinomycin D, 1 microgram/mL), a NOS inhibitor (L-N G-nitroarginine methyl ester [L-NAME], 1 mM), and L-NAME plus L-arginine (5 mM). Furthermore, PBMCs were incubated with or without addition of therapeutic concentrations of hydrocortisone (15 micrograms/mL). Culture supernatants were collected and assayed for NO production. NO production was significantly elevated in asthmatics compared with the control group (1.39 ± 0.21 micromoles versus 0.46 ± 0.01 micromoles; P < .05). L-NAME significantly reduced NO production in asthmatics (0.83 ± 0.06 micromoles; P < .05), an effect completely reversed by L-arginine. Theophylline blocked NO production in asthmatics (1.39 ± 0.21 micromoles to 0.92 ± 0.11; P < .05). There was no significant effect with any of the other medications. This study suggests that theophylline may be antiinflammatory by inhibiting the L-arginine-dependent production of NO in patients wih asthma.