An inflammatory reaction could be an important source of intraindividual variability in cyclosporine pharmacokinetics, possibly through an inhibition of cytochrome P4503A-dependent enzyme activities by endogenous interleukin-6. Blood AM1 accumulation might be explained by a secondary metabolic step that is highly sensitive to the inhibitory effect of interleukin-6.

A study has been made of the exudate provoked by intrapleural carrageenan in rats. Various parameters have been measured including volume of exudate, numbers and types of cells. Pharmacological assay has shown the early release of histamine and 5HT into the exudate followed at later times by a release of prostaglandins, and a second release of histamine. The role of complement has been studied. Intrapleural injection of carrageenan after complement depletion produced a reduced migration of polymorphonuclear cells and also a reduction in volume of exudate. Prostaglandins remained unaffected by this treatment.

Cetirizine was first described as a specific anti-H1 molecule displaying potent antiallergic activity. It was later found that its pharmacological properties extended to cellular actions as on eosinophil recruitment at inflammatory sites in allergic patients. Monocytes and macrophages participate in allergic mechanisms, particularly through high affinity H1 and H2 membrane receptors and generation of pro- and anti-inflammatory agents; among them histamine-induced factors, IL-1 and prostanoids are of importance. The aim of this work was to investigate the effect exerted by various concentrations of cetirizine (0.1-10 micrograms/ml) applied in vitro to human monocytes and peritoneal rat macrophages cultured for 24 h. Peritoneal macrophages were collected either from normal or experimentally inflamed rats. Human monocytes, isolated from peripheral blood, were studied either in a resting state or after stimulation by LPS from Escherichia coli (1 and 10 micrograms/ml). Cetirizine (10 micrograms/ml) significantly enhanced IL-1 release by human monocytes stimulated by a weak LPS concentration (1 microgram/ml) but could not modify the maximal increase of IL-1 release induced by 10 micrograms/ml of LPS. It did not exert any effect on resting cells. Cetirizine (0.1-10 micrograms/ml) enhanced PGE2 release by resting human monocytes. Concentrations of 1 and 10 micrograms/ml enhanced PGE2 release by LPS-stimulated monocytes, and by healthy and inflamed rat macrophages. This effect was concentration-dependent. Our findings point to an anti-inflammatory action of cetirizine via PGE2 release and histamine H2 interactions. Cetirizine did not directly modify IL-1 generation by resting monocytes but the IL-1 production observed after LPS stimulation could promote the mechanisms by which PGE2 is released.