Differential inhibition of equine neutrophil function by phosphodiesterase inhibitors

• Published in: Journal of veterinary pharmacology and therapeutics 2001-08, Vol.24 (4), p.275-281
• Main Authors: Rickards, K. J., Page, C. P., Lees, P., Cunningham, F. M.
• Format: Article
• Language: English
• Subjects: Animals; Cell Adhesion - drug effects; Cells, Cultured - drug effects; Horse Diseases - drug therapy; Horses - metabolism; Lung Diseases, Obstructive - drug therapy; Lung Diseases, Obstructive - veterinary; Neutrophils - drug effects; Neutrophils - physiology; Phosphodiesterase Inhibitors - pharmacology; Phosphodiesterase Inhibitors - therapeutic use; Rolipram - pharmacology; Rolipram - therapeutic use; Superoxides - metabolism; Theophylline - pharmacology; Theophylline - therapeutic use
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1046/j.1365-2885.2001.00344.x

Rickards, K. J., Page, C. P., Lees, P., Cunningham, F. M. Differential inhibition of equine neutrophil function by phosphodiesterase inhibitors J. vet. Pharmacol. Therap.24, 275–281. Neutrophils are recruited to the lungs of horses with chronic obstructive pulmonary disease (COPD) and exhibit increased activity after antigen challenge, which may contribute to inflammation and lung damage. Inhibition of phosphodiesterase isoenzymes (PDEs) has been shown to attenuate human neutrophil functions including superoxide production, leukotriene (LT)B4 biosynthesis, enzyme and chemokine release. As equine neutrophils contain predominantly the isoenzyme, PDE4, the present study was undertaken to investigate the effects of rolipram, a PDE4 inhibitor, on equine neutrophil function. For comparison, the effects of the nonselective PDE inhibitor, theophylline, were examined. Cells from both normal horses and COPD horses in remission were used. Superoxide production was significantly inhibited by both rolipram [32.2 ± 2.6 vs. 10.1 ± 1.1 nmol/106 cells and 49.8 ± 6.8 vs. 22.7 ± 2.2 nmol/106 cells for normal and COPD susceptible horses, respectively, in response to 10–7 M human recombinant (hr) C5a] and theophylline (19.0 ± 0.6 vs. 10.2 ± 0.6 nmol/106 cells and 24.3 ± 2.1 vs. 10.7 ± 0.9 nmol/106 cells for normal and COPD susceptible horses, respectively, in response to 10–7 M C5a). However, superoxide production induced by serum treated zymosan was inhibited only by theophylline (10–3 M). Neither hrC5a‐ nor platelet activating factor (PAF)‐induced neutrophil adherence to fibronectin coated plastic was reduced by rolipram (10–5 M). These results demonstrate that the effects of PDE inhibitors on equine neutrophils are both stimulus and function dependent. The PDE4 inhibitors may reduce neutrophil activation in vivo in horses with COPD.