Synergistic effect of theophylline and procaterol on interleukin-5-induced degranulation from human eosinophils.
Inhibiting the release of toxic granule proteins from eosinophils is a possible means of treating allergic inflammation. This study was performed to examine whether procaterol and theophylline, commonly used bronchodilators in asthma, inhibit eosinophil degranulation induced by interleukin (IL)-5. Purified eosinophils from patients with asthma were incubated with IL-5 for 24 hr in the presence of theophylline, procaterol, combinations of theophylline and procaterol, or dexamethasone. Levels of eosinophil-derived neurotoxin (EDN) in the supernatants were measured with radioimmunoassay. Theophylline inhibited IL-5-induced release of EDN in a concentration-dependent manner. Procaterol inhibited degranulation only at high concentrations. However, procaterol at 10(-9) M and 10(-8) M, which are physiologic concentrations, together with theophylline at 10(-5) M, which is a concentration commonly found in the serum of patients receiving low-dose theophylline, inhibited degranulation by 43.8%. This finding indicates that theophylline and procaterol have synergistic effects. The inhibition was comparable to that with dexamethasone at 10(-9) M. Our results suggest that a combination of low-dose theophylline and procaterol exhibits antiinflammatory effects in asthma by inhibiting eosinophil-effector functions.
Fujisawa
Takao
T
Department of Pediatrics and Allergy, National Mie Hospital, Tsu City, Japan. fujisawa@mie.hosp.go.jp
Kato
Yoshiko
Y
Terada
Akihiko
A
Iguchi
Kosei
K
Kamiya
Hitoshi
H
D001993:Bronchodilator Agents / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D004804:Eosinophils / Q000502:physiology*; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology*; D017265:Procaterol / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology*
D001993:Bronchodilator Agents; D015848:Interleukin-5; D003907:Dexamethasone; D013806:Theophylline; D017265:Procaterol