An Appraisal of the Interrelationships Between Prostaglandins and Cyclic Nucleotides in Inflammation

The evidence supporting the role of prostaglandins and cyclic nucleotides "in vitro" has been reviewed. The pro-inflammatory role of prostaglandins of the E series (PGE) is typified by its ability to induce increased vascular permeability. Prostaglandins of the F series (PGF) may be anti-inflammatory via their inhibitory effect on increased vascular permeability. However, a paradox exists which suggests that PGE may also be anti-inflammatory via its stimulatory effect on cyclic AMP synthesis as shown "in vitro" (e.g. decreased leucocyte lysosomal enzyme secretion; decreased lymphocyte cytotoxicity and mitosis; decreased release of mediators from sensitized tissues during anaphylaxis). Conversely PGF is capable of stimulating cyclic GMP which augments the processes listed above, and may therefore be termed pro-inflammatory. An attempt has been made to correlate these findings with "in vivo" studies which support the anti-inflammatory role of cyclic GMP. However, the significance of PGE and PGF in the inflammatory response "in vivo" appears to be more complex. It is suggested that greater emphasis should be placed on the "in vivo" study of beta-adrenergic and cholinergic mediators, substances which induce the anti- and pro-inflammatory effects of cyclic AMP and cyclic GMP "in vitro", respectively.