In vitro effect of cetirizine on PGE2 release by rat peritoneal macrophages and human monocytes

Abstract

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.

Addressing Androgenetic Alopecia-A Complex Disorder-with a Multilateral Treatment Strategy

“…Cetirizine a second generation anti-histaminic agent and more specifically an H1 receptor blocker has been observed to reduce PGD2 release from mast cells, 71 whereas, increase the release of PGE2 in a concentrationdependent manner, from human monocytes in in vitro setting. 72 Based on this observations another study designed to evaluate the efficacy of topical 1% cetirizine solution reported significant improvement in hair growth in patients with mild to moderate AGA. 73 In addition, the anti-inflammatory and anti-allergic activities of cetirizine can be useful in AGA patients with scalp irritation and inflammation.…”

“…VDR expression has been linked to reduced proliferation and heightened differentiation of keratinocytes which assist in efficient hair cycle progression. 72 Expression of VDR is of more significance for the keratinocyte stem cells located in follicular bulge as any dysfunctionalities in VDR may result in hair cycle progression defects. 74 In fact, the expression of VDR in keratinocytes has been associated with and varies depending on the specific stage of the hair cycle the follicle is in.…”

Cetirizine and allopurinol as novel weapons against cellular autoimmune disorders

“…The drug has been shown to induce the release of PGE2 from rat peritoneal macrophages and human monocytes [13]; PGE2 exerts a suppressive effect on macrophage functions such as antigen presentation and MHC class II expression [14].…”

Polysaccharide peptides from COV-1 strain of Coriolus versicolor induce hyperalgesia via inflammatory mediator release in the mouse

“…The cells were incubated for 12 h, then cell medium was collected and stored at À 70 -C for analysis. Compound 48/80 (1 Ag/ml) and LPS (10 Ag/ml) were used as positive controls for mediators release (Roch-Arveiller et al, 1994). Mediator concentrations were measured by commercial ELISA kits, with sensitivity at 0.1 pg/ml.…”