E-TYPE PROSTAGLANDINS ENHANCE LOCAL EDEMA FORMATION AND NEUTROPHIL ACCUMULATION BUT SUPPRESS EOSINOPHIL ACCUMULATION IN GUINEA-PIG SKIN

1 Prostaglandins possess both pro- and anti-inflammatory actions depending on their route of administration and the experimental model used. In this study, we have investigated the effect of locally injected prostaglandins on oedema formation, neutrophil accumulation and eosinophil accumulation in inflammatory responses in guinea-pig skin. 2 Prostaglandin E1 (PGE1) significantly enhanced local oedema formation induced by zymosan-activated plasma (ZAP), bradykinin and in a passive cutaneous anaphylatic (PCA) reaction. The accumulation of ZAP-induced In-111-labelled neutrophils was also significantly enhanced by PGE1. In addition, the prostacyclin analogue, iloprost, enhanced ZAP-induced responses. 3 In contrast PGE1 decreased the accumulation of In-111-labelled eosinophils in skin sites. This was demonstrated on eosinophil accumulation and local eodema formation induced by PAF, compound 48/80 and in the PCA reaction. PGE2 also suppressed eosinophil accumulation while iloprost had no detectable effect. 4 Isoprenaline inhibited eosinophil accumulation in a dose-dependent manner with no effect on local oedema formation, except in the case of responses to ZAP where suppression was observed. 5 The vasodilator neuropeptide, calcitonin gene-related peptide (CGRP), enhanced local oedema formation but had no detectable effect on eosinophil accumulation. 6 In conclusion, the magnitude of a given response to an inflammatory mediator in vivo depends on the net effect of stimulation of several cell types e.g. arteriolar smooth muscle cells, microvascular endothelial cells, mast cells and accumulating leukocytes. In this study, we have demonstrated that different components of the inflammatory response in guinea-pig skin can be differentially modulated by E-type prostaglandins and isoprenaline, suggesting that cyclic AMP has an important regulatory role.