Theophylline inhibits the production of nitric oxide by peripheral blood mononuclear cells from patients with asthma.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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 microg/mL), a NOS inhibitor (L-NG-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 microg/mL), theophylline (15 microg/mL), albuterol (15 microg/mL) and ipratropium bromide (12 microg/mL). Culture supernatants were collected and assayed for NO production.


RESULTS
NO production was significantly elevated in asthmatics compared with the control group (1.39+/-0.21 microM versus 0.46+/-0.01 microM; P < .05). L-NAME significantly reduced NO production in asthmatics (0.83+/-0.06 microM; P < .05), an effect completely reversed by L-arginine. Theophylline blocked NO production in asthmatics (1.39+/-0.21 microM to 0.92+/-0.11; P < .05). There was no significant effect with any of the other medications.


CONCLUSIONS
This study suggests that theophylline may be antiinflammatory by inhibiting the L-arginine-dependent production of NO in patients with asthma.
Department of Pathology, Nassau County Medical Center, State University of New York at Stony Brook, East Meadow 11554, USA.
G R
GR
Sansone
A
A
Matin
S F
SF
Wang
D
D
Bouboulis
M
M
Frieri
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D013806:Theophylline / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D009569:Nitric Oxide; D013806:Theophylline