Histamine-Induced Activation of Human Lung Macrophages

Marone, Gianni; Gentile, Marco; Petraroli, Angelica; Rosa, N.; Triggiani, Massimo

doi:10.1159/000053725

Cited by 37 publications

(33 citation statements)

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“…As an example, in line with our observations, histamine via H2R, has been shown to inhibit the cytokine response to microbial products of monocytes [28,32] and dendritic cells [33]. Differentiation of monocytes into macrophages, on the other hand, induces the preferential expression of H1R over H2R [34], leading to increased production of IL-8 upon exposure to histamine [35]. Therefore, the response to histamine can greatly vary among different cells, depending on expression profile of histamine receptors and among different individuals, possibly depending on genetic variation of histamine receptors [36].…”

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confidence: 86%

IgE and IL‐33−mediated triggering of human basophils inhibits TLR4−induced monocyte activation

et al. 2014

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Basophils are circulating granulocytes, best known as effector cells in allergic reactions.Recent studies in mice suggest that they might also participate in the suppression of chronic inflammation. The aim of this study was to assess the ability of purified human basophils to modulate monocyte responses upon IL-33 and IgE triggering. Activation of human basophils with IL-33 induced the production of IL-4 and the release of histamine, and enhanced their IgE-mediated activation. In addition, basophils triggered with IL-33 and anti-IgE significantly suppressed the LPS-induced production of the proinflammatory cytokine TNF-α and the upregulation of the costimulatory molecule CD80 by monocytes. These effects were mainly explained by the release of histamine, as they could be inhibited by the histamine receptor 2 antagonist ranitidine, with a smaller contribution of IL-4. In contrast, basophil-derived IL-4 and histamine had opposing effects on the expression of the inhibitory Fc γ receptor IIb and the production of IL-10 by monocytes. Our data show that basophils can influence monocyte activation and suggest a previously unrecognized role for human basophils in the modulation of monocyte-mediated immune responses, through the balanced secretion of histamine and IL-4.Keywords: Basophils r Cellular activation r Histamine r Immune regulation r Monocytes Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionBasophils are circulating granulocytes, representing less than 1% of peripheral blood leukocytes. They are classically known for their involvement as effector cells in allergic reactions [1][2][3]. Because of their paucity and the difficulty in isolating them, there is still relatively little information available on their functions and potential immunomodulatory effects [4]. Studies in mice suggest a possible role for basophils in the induction of adaptive immunity in the context of Th2 responses, where they have been shown to be the major producers of , although their function as Correspondence: Dr. Felice Rivellese e-mail: rivelles@gmail.com antigen presenting cells and their dispensability in the induction of Th2 responses are still under debate [6,7]. In addition, recent experimental data showed how these rare leukocytes might also exert anti-inflammatory effects in the context of autoimmune and allergic inflammation. In a mouse model of arthritis, basophils have been implicated in the immunosuppressive response mounted upon injection of intravenous immunoglobulin (IVIG) [8]. Briefly, the authors proposed the following scenario to elucidate IVIG-mediated immune suppression: myeloid-derived cells, in response to the sialylated fraction of IVIG, release IL-33, which, in turn, activates basophils to produce IL-4. Finally, basophil-derived IL-4 induces the upregulation of the inhibitory Fc γ Receptor (FcγRIIb) on inflammatory macrophages, leading to the suppression of antibody-dependent inflammation. Thus, IL-33www.eji-journal.eu 3046 Felice R...

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IgE and IL‐33−mediated triggering of human basophils inhibits TLR4−induced monocyte activation

et al. 2014

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“…20,22,33 The effect of fexofenadine on nasal congestion might reflect an activity that is broader than its antagonism at the H 1 -receptor. Numerous in vitro studies with fexofenadine have highlighted the potential of this agent to produce significant anti-inflammatory effects at clinically relevant concentrations, [34][35][36][37][38] and it is hypothesized that these effects might contribute to inhibition of the late-phase response. 37 In this large pediatric population, the incidence and severity of reported adverse events with fexofenadine were similar to those for placebo.…”

Section: Discussionmentioning

confidence: 99%

Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal allergic rhinitis

Wahn¹,

Meltzer²,

Finn³

et al. 2003

Journal of Allergy and Clinical Immunology

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Background: This is the first prospective, randomized, doubleblind, placebo-controlled study showing statistical improvement of an H 1 -antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. Objective: This randomized, placebo-controlled, parallelgroup, double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. Methods: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (±1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point.Results: Fexofenadine was significantly superior to placebo in the primary efficacy analysis (P ≤ .0001). Individual symptom scores showed statistically significant superiority compared with placebo (P < .05), including nasal congestion in the evening reflective assessment (P < .05). There was no significant difference in adverse events between fexofenadine and placebo, either overall or by causality.

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“…Fexofenadine is a potent, selective, non-sedating, H 1 -receptor antagonist with proven efficacy in the relief of clinical symptoms of AR, including nasal congestion [11, 12, 13, 14, 15, 16, 17, 18]. In addition to its anti-allergic effects, fexofenadine has anti-inflammatory properties at clinically relevant concentrations [19, 20, 21]. Furthermore, health outcome studies have shown that fexofenadine HCl 60 mg twice daily (b.i.d.)…”

Section: Introductionmentioning

confidence: 99%

Fexofenadine Improves the Quality of Life and Work Productivity in Japanese Patients with Seasonal Allergic Rhinitis during the Peak Cedar Pollinosis Season

Okubo

Gotoh

Shimada

et al. 2005

Int Arch Allergy Immunol

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Background: Although currently in its infancy, quality of life (QOL) research in Japan is rapidly expanding and is expected to become a standard outcome measure in clinical trials. In Japan, QOL has not previously been assessed in patients with allergic rhinitis (AR); we report the first clinical study applying the recently validated Japanese translations of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) Questionnaire to assess the effects of the oral antihistamine, fexofenadine, on QOL and work productivity due to cedar pollinosis. Patients and Methods: A randomized, double-blind, placebo-controlled, single-site study was conducted during the peak cedar pollinosis season in Japan. After a 7-day run-in period, subjects were randomized to receive fexofenadine HCl 60 mg twice daily (bid) or placebo for 2 weeks. Results: Overall, 206 Japanese subjects with AR were included in the intention-to- treat population (fexofenadine, n = 104, and placebo, n = 102). Fexofenadine statistically significantly improved overall QOL compared with placebo (p = 0.005) and improvements were reported in the RQLQ domains: activities (p = 0.047), practical problems (p = 0.003), nasal symptoms (p = 0.003) and eye symptoms (p ≤ 0.001). Clinically significant improvements in practical problems, eye symptoms and activity limitations, exceeding the 0.05 level, were observed with fexofenadine. These improvements in QOL were associated with significant symptom relief (p < 0.001 vs. placebo). Improvements in impairment at work were also reported with fexofenadine. Conclusion: In Japan, this is the first clinical study to show that fexofenadine HCl (60 mg b.i.d.) improves overall QOL and work productivity in patients with seasonal AR using validated Japanese instruments.

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Histamine-Induced Activation of Human Lung Macrophages

Cited by 37 publications

References 18 publications

IgE and IL‐33−mediated triggering of human basophils inhibits TLR4−induced monocyte activation

IgE and IL‐33−mediated triggering of human basophils inhibits TLR4−induced monocyte activation

Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal allergic rhinitis

Fexofenadine Improves the Quality of Life and Work Productivity in Japanese Patients with Seasonal Allergic Rhinitis during the Peak Cedar Pollinosis Season

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