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Effects of phosphodiesterase isoenzyme inhibitors on cutaneous inflammation in the guinea‐pig
Author(s) -
Teixeira M.M.,
Rossi A.G.,
Williams T.J.,
Hellewell P.G.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13073.x
Subject(s) - rolipram , histamine , eosinophil , phosphodiesterase , zaprinast , pharmacology , chemistry , inflammation , systemic administration , guinea pig , allergic inflammation , phosphodiesterase inhibitor , immunology , medicine , asthma , biochemistry , biology , enzyme , microbiology and biotechnology , in vivo
1 Inflammation is central to the pathophysiology of asthma. The recent findings that different inflammatory cells may express different phosphodiesterase (PDE) isoenzymes have centred attention on inhibitors of these isoenzymes as new drugs for the treatment of asthma. In this study, we investigated the effect of different PDE isoenzyme inhibitors on the accumulation of 111 In‐labelled eosinophils and local oedema formation at sites of allergic‐ and mediator‐induced inflammation in guinea‐pig skin. 2 Systemic treatment with SK&F 94120, a type III PDE inhibitor, or zaprinast, a type V PDE inhibitor, had no effect on the 111 In‐eosinophil accumulation and oedema formation induced by i.d. injection of zymosan‐activated plasma (ZAP), PAF, histamine or in a passive cutaneous anaphylaxis (PCA) reaction. 3 Systemic treatment with rolipram, a type IV PDE inhibitor, effectively inhibited 111 In‐eosinophil accumulation induced by ZAP, PAF, histamine and in a PCA reaction. However, oedema formation measured in the same sites was not affected. Systemic administration of higher doses of theophylline produced similar results. In contrast, 111 In‐neutrophil accumulation induced by ZAP or in a PCA reaction was not altered by systemic treatment with rolipram. 4 Locally‐injected rolipram had little effect on 111 In‐eosinophil accumulation and oedema formation induced by histamine, PAF and in a PCA reaction. 5 These data show that systemic, but not local, treatment with rolipram effectively inhibits allergic‐ and mediator‐induced 111 In‐eosinophil accumulation but not oedema formation or 111 In‐neutrophil accumulation. This, taken together with the potent inhibitory effects of PDE type IV inhibitors on eosinophil function in vitro , suggest that this class of drugs may be beneficial in disease states such as asthma where eosinophils are thought to play a major pathophysiological role.