In vitro effect of cetirizine on PGE2 release by rat peritoneal macrophages and human monocytes. Effect of ZCR-2060, an antiallergic agent, on antigen-induced immediate- and late-phase increases in airway resistance in sensitized guinea pigs. [Effect of cetirizine therapy on the rate of adverse reactions to specific desensitization] Rx drugs

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Agents Actions. 1994 Nov;43(1-2):13-6.
In vitro effect of cetirizine on PGE2 release by rat peritoneal macrophages and human monocytes.

Roch-Arveiller M, Tissot M, Idohou N, Sarfati G, Giroud JP, Raichvarg D.

Departement de Pharmacologie, CNRS URA 1534, Paris, France.

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.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7741033&dopt=Abstract

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Int Arch Allergy Immunol. 1995 Jan;106(1):78-85.
Effect of ZCR-2060, an antiallergic agent, on antigen-induced immediate- and late-phase increases in airway resistance in sensitized guinea pigs.

Abe T, Yoshida K, Omata T, Segawa Y, Matsuda K, Nagai H.

Department of Pharmacology, Gifu Pharmaceutical University, Japan.

The effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060) on passive systemic anaphylaxis (PSA) and antigen-induced immediate- and late-phase increase in airway resistance (Rrs) in either passively or actively sensitized guinea pigs were investigated. ZCR-2060 inhibited PSA in guinea pigs. ID50 values of ZCR-2060, ketotifen, terfenadine and cetirizine on PSA were 0.03, 0.02, 0.8 and 0.3 mg/kg, respectively, when administered orally 1 h before the antigen challenge. The protective effect of ZCR-2060 was observed until 12 h before the antigen challenge. Aeroantigen-induce immediate increase in Rrs in passively sensitized guinea pigs with and without metyrapone treatment was inhibited by ZCR-2060, ketotifen, terfenadine and cetirizine. In contrast, prednisolone did not affect the aeroantigen-induced immediate increase in Rrs in animals not treated with metyrapone, but significantly inhibited the metyrapone-induced enhanced immediate response. In actively sensitized animals, the immediate- and late-phase increases in Rrs were observed within 30 min and between 3 and 8 h after the aeroantigen challenge. Pretreatment with metyrapone accelerated both antigen-induced responses. ZCR-2060 (1 mg/kg) significantly inhibited both responses. Ketotifen (1 mg/kg), terfenadine (10 mg/kg) and prednisolone (10 mg/kg) significantly the inhibited the late-phase response, but did not affect the immediate-phase response. In contrast, Cetirizine (10 mg/kg) did not affect either response. The effect of ZCR-2060 on late-phase response was stronger than that of ketotifen, terfenadine and cetirizine, and was almost the same as that of prednisolone. These results suggest that ZCR-2060 has a potent protective effect on immediate- and late-phase increases in Rrs.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7812169&dopt=Abstract

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Pol Tyg Lek. 1994 Apr 4-11;49(14-15):337-40.
[Effect of cetirizine therapy on the rate of adverse reactions to specific desensitization]

[Article in Polish]

Kruszewski J, Zaras E.

Kliniki Chorob Zakaznych Instytutu Medycyny Wewnetrznej Centralnego Szpitala Klinicznego WAM, Warszawie.

An effect of cetirizine--one of antihistaminic agents--on the rate of adverse reactions to the specific desensitization has been evaluated in patients with atopic respiratory diseases. The study included 270 patients desensitized in 1988-1993 for the atopic diseases due to hypersensitivity to grass pollens and Dermatophagoides pteronyssinus. Standard Alvac-P. Pollinex, and Alvac-S HDM vaccines have been used. Occurrence and severity of the adverse reactions noted during 3,368 injections of vaccines have been analysed. Frequency and adverse reactions severity have been compared for two periods--1988-1990 when patients have not been given antihistaminic agent, and 1991-1993--when ceterizine has been administered during the whole period of desensitization. It has been found that simultaneous cetirizine administration decreases frequency and severity of adverse reaction to the used vaccines. Such a procedure may be recommended to patients with advance hypersensitivity given vaccines in out-patient clinics.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7854995&dopt=Abstract

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