Beyond the histamine receptor: effect of antihistamines on mast cells

Fm, Cuss

doi:10.1046/j.1365-2222.1999.00013.x

Cited by 23 publications

(19 citation statements)

References 30 publications

(36 reference statements)

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“…20 The in vitro effects of antihistamines on the inhibition of mediator release from mast cells have been reported. 21 Moreover, an in vitro study of human conjunctival mast cells revealed that epinastine inhibited mast cell secretion of cytokines, including IL10. 22 However, it remains unclear why antihistamines inhibit cytokine secretion, although H1 antagonism seems unrelated.…”

Section: Discussionmentioning

confidence: 99%

T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease

et al. 2014

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IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffinembedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFb1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease pathogenesis.

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Section: Discussionmentioning

confidence: 99%

T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease

et al. 2014

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“…Moreover, fexofenadine undergoes minimal systemic metabolism and is well tolerated, also in patients with renal or hepatic impairment and in the elderly. It appears to be associated with no risk of significant drug interactions (12)(13)(14)(15).Recent studies have shown that antihistamines can also exert antiinflammatory and antiallergic actions (16)(17)(18)(19)(20). /11 vitro evidences have demonstrated that fexofenadine may modulate the release of pro-inflammatory mediators and adhesion molecules from human nasal epithelial cells (21)(22).…”

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confidence: 99%

“…Recent studies have shown that antihistamines can also exert antiinflammatory and antiallergic actions (16)(17)(18)(19)(20). /11 vitro evidences have demonstrated that fexofenadine may modulate the release of pro-inflammatory mediators and adhesion molecules from human nasal epithelial cells (21)(22).…”

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confidence: 99%

Fexofenadine in Chronic Idiopathic Urticaria: A Clinical and Immunohistochemical Evaluation

Cassano

Filieri

et al. 2002

Int J Immunopathol Pharmacol

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Fexofenadine is a non-sedating selective third-generation antihistamine, which also exerts an antiinflammatory action. The aim of this study was to evaluate the influence on the expression of inflammatory skin mediators, together with the efficacy and tolerability, of fexofenadine in chronic idiopathic urticaria (CIU). Fexofenadine 180mg was administered once daily for 4 weeks after a placebo run-in phase of3 to 7 days. Efficacy paramaters were obtained from patients' assessment of urticaria symptoms. Non-Iesional skin of patients with active CIU was studied immunohistochemically before and after treatment. The expression of the following mediators was evaluated: adhesion molecules (ICAM-l, ELAM-l, VCAM-l)j mast cell proteases (chymase and tryptase) and proinflammatory cytokines (IL-l~, IL-3, IL-6 and TNF-n). Of the 20 subjects enrolled, 3 dropped out of the study. Treatment proved successful in most cases (88.2 %) (p <0.01) and a significant improvement of all symptoms was registered. Treatment was well-tolerated by all patients; adverse events, neither serious nor drug-related, occurred in any case. Immunochemistry revealed at the baseline a significant expression of ELAM-l, VCAM-l, tryptase, chymase, and TNF-« (p~0.05) in non-Iesional skin of patients compared to normal controls. After treatment with fexofenadine, there was a significant decrease in the expression of ELAM-l (p= 0.02), VCAM-l (p= 0.04) and tryptase (p=0.04), whereas no relevant change was observed for the other parameters examined. This work confirms the efficacy and tolerability of fexofenadine HCI 180mg in CIU. These preliminary data show a trend towards a decrease in the expression of tryptase and some adhesion molecules after treatment, suggesting an anti-inflammatory activity of fexofenadine.Chronic idiopathic urticaria (CIU) is defined as the occurrence of wheals on most days for more than six weeks in the absence of any known causative or triggering agents (1). As it is not possible to adopt specific measures of prevention in CIU, treatment hangs upon symptomatic tools, with HI antihistamines as the mainstay for patients with uncomplicated forms (2-3). Newgeneration antihistamines are usually preferred owing to the greater affinity for H 1 receptors and the lower incidence of sedation and anticholinergic effects compared with older molecules (4-5).Fexofenadine is a non-sedating third generation antihistamine with highly selective H 1-receptor antagonist activity, which has been approved for the treatment of seasonal allergic rhinitis and CIU. Controlled studies have proved the high therapeutic value and the excellent tolerability offexofenadine (6-11). The good safety profile of fexofenadine is also due to the absence of cardiotoxic effects and sedation, even at doses much higher than those recommended for aller- gic rhinitis and CIU. Moreover, fexofenadine undergoes minimal systemic metabolism and is well tolerated, also in patients with renal or hepatic impairment and in the elderly. It appears to be associated with no risk of signifi...

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“…Apesar disso, já se sabe, há algum tempo, que, além de atuarem sobre os receptores H1, muitos anti-H1, em doses apropriadas, são capazes de inibir não somente a liberação de histamina por mastócitos, 9,10 como também a própria ativação mastocitária 11 . Alguns deles podem ainda regular a expressão e/ou a liberação de citocinas, quimocinas, moléculas de adesão e mediadores inflamatórios 5,8 .…”

Section: Efeitos Antialérgicos -Antiinflamatóriosunclassified

New antihistamines: a critical view

Camelo-Nunes¹

2006

J Pediatr (Rio J)

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Objective: To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders.Sources: Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines.Summary of the findings: Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit antiinflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals. Conclusions:On the basis of the evidence on H1 antihistamines, none of them deserve the title third-generation antihistamine. As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS. J Pediatr (Rio J). 2006;82(5 Suppl):S173-80: Antihistamines, desloratadine, fexofenadine, levocetirizine, rupatadine. ResumoObjetivo: Avaliar criticamente os mais novos anti-histamínicos anti-H1 e os diferentes termos utilizados para denominá-los, com base na revisão de evidências sobre o papel dos anti-H1 no tratamento das doenças alérgicas.Fontes dos dados: Artigos originais, revisões e consensos indexados nos bancos de dados MEDLINE e PUBMED de 1998 a 2006. Palavra chave: anti-histamínicos.

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Beyond the histamine receptor: effect of antihistamines on mast cells

Cited by 23 publications

References 30 publications

T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease

T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease

Fexofenadine in Chronic Idiopathic Urticaria: A Clinical and Immunohistochemical Evaluation

New antihistamines: a critical view

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