Inhibition of cytokine generation and mediator release by human basophils treated with desloratadine

Schroeder, John T.; Schleimer, Robert P.; Lichtenstein, L M; Kreutner, William

doi:10.1046/j.1365-2222.2001.01130.x

Cited by 96 publications

(57 citation statements)

References 26 publications

(23 reference statements)

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“…An H 1 antihistamine such as desloratadine could potentially decrease allergen-IgE-induced mast cell activation by reducing NF-ĸB activity via H 1 receptor inverse agonism. Indeed, reduced mast cell and basophil activation and cytokine release in response to anti-IgE or calcium ionophore have been demonstrated with desloratadine in a variety of in vitro models [34, 35]. The mechanism by which desloratadine acts at the H 1 receptor is probably linked to alterations in intracellular calcium concentrations.…”

Section: Discussionmentioning

confidence: 99%

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Desloratadine Inhibits Constitutive and Histamine-Stimulated Nuclear Factor-κB Activity Consistent with Inverse Agonism at the Histamine H<sub>1</sub> Receptor

Wu¹,

Anthes²,

Kreutner³

et al. 2004

Int Arch Allergy Immunol

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Background: The human histamine H₁ receptor is constitutively active and exhibits basal activation of nuclear factor-ĸB (NF-ĸB), an important modulator of allergic inflammation. Certain H₁ antihistamines have recently been shown to inhibit basal NF-ĸB activity by stabilizing the H₁ receptor in an inactive state, a phenomenon called ‘inverse agonism’. Methods: We evaluated the effect of the new H₁ antihistamine, desloratadine, on basal and histamine-stimulated NF-ĸB activity and compared it with the activities of other H₁ antihistamines. Results: Transiently transfected COS-7 cells co-expressing NF-ĸB-luciferase and the H₁ receptor exhibited constitutive NF-ĸB activity. H₁ antihistamines reduced basal NF-ĸB activity (rank order of potency: desloratadine > pyrilamine > cetirizine > loratadine > fexofenadine). Histamine stimulated basal NF-ĸB activity 8-fold, which was blocked by H₁ antihistamines (rank order of potency: desloratadine > cetirizine > pyrilamine > loratadine > fexofenadine). Neither histamine nor antihistamines had any effect on NF-ĸB activity in the absence of the H₁ receptor. Conclusions: Desloratadine, acting through the histamine H₁ receptor, inhibited basal NF-ĸB activity and can thus be classified as an inverse agonist. Inhibition of basal and histamine-stimulated NF-ĸB activity may help to explain previously reported inhibitory effects of desloratadine on allergic inflammatory mediators.

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Section: Discussionmentioning

confidence: 99%

“…Desloratadine reduces the generation of the cytokines IL-4/IL-13 [34], IL-6, IL-8 [38]and the adhesion molecules P-selectin [39]and ICAM-1 [40]from human basophils, mast cells and endothelium in vitro. Some of these effects were demonstrated at nanomolar or subnanomolar concentrations, which indicates that they may be clinically relevant.…”

Section: Discussionmentioning

confidence: 99%

Desloratadine Inhibits Constitutive and Histamine-Stimulated Nuclear Factor-κB Activity Consistent with Inverse Agonism at the Histamine H<sub>1</sub> Receptor

Wu¹,

Anthes²,

Kreutner³

et al. 2004

Int Arch Allergy Immunol

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“…However, broader antiinflammatory effects have been ascribed to H1R blockers, including inhibitory effects on adhesion molecule expression (21,22) and inhibition of eosinophil chemotaxis (23). An H1R antagonist has also been shown to inhibit the generation of IL-4 and IL-13 by human basophils (24). We and others have recently shown that H1R antagonists prevent allergen-induced airway inflammation and hyperreactivity (25)(26)(27), but the cellular immunologic basis of this effect has not been clearly established.…”

Section: Introductionmentioning

confidence: 99%

The H1 histamine receptor regulates allergic lung responses

Bryce¹

2006

Journal of Clinical Investigation

123

100

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Histamine, signaling via the type 1 receptor (H1R), has been shown to suppress Th2 cytokine production by in vitro cultured T cells. We examined the role of H1R in allergic inflammation in vivo using a murine asthma model. Allergen-stimulated splenic T cells from sensitized H1R -/-mice exhibited enhanced Th2 cytokine production. Despite this Th2 bias, allergen-challenged H1R -/-mice exhibited diminished lung Th2 cytokine mRNA levels, airway inflammation, goblet cell metaplasia, and airway hyperresponsiveness (AHR). Restoration of pulmonary Th2 cytokines in H1R -/-mice by intranasal IL-4 or IL-13 restored inflammatory lung responses and AHR. Further investigation revealed that histamine acts as a T cell chemotactic factor and defective T cell trafficking was responsible for the absence of lung inflammation. Cultured T cells migrated in response to histamine in vitro, but this was ablated by blockade of H1R but not H2R. In vivo, allergen-specific WT but not H1R -/-CD4 + T cells were recruited to the lungs of naive recipients following inhaled allergen challenge. H1R -/-T cells failed to confer airway inflammation or AHR observed after transfer of WT T cells. Our data establish a role for histamine and H1R in promoting the migration of Th2 cells into sites of allergen exposure.

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“…Loratadine increases the cytosolic calcium by releasing it from intracellular stores (calcium activates NF-kB, increases the cytokines release), partially inhibits the leukotrienes as Letari et al [24] assessed in their research performed in vitro on rat peritoneal macrophages. Naclerio [25] in a study performed on nasal challenge antigen model and Shroeder et al [26] in their research in vitro on human basophils established that loratadine reduces the release of histamine and PGD 2, but not significantly. The anti-inflammatory effects of loratadine are not efficient in reducing the inflammation, and it promotes a supplementary oxidative stress in the inflamed tissue.…”

Section: Livermentioning

confidence: 99%

Resveratrol and Loratadine Effects on Oxidative Stress Induced by Experimental Inflammation

Mitrea¹,

Clichici²,

Filip³

et al. 2017

Studia UBB Chemia

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ABSTRACT.Resveratrol is a polyphenol with important antioxidant and antiinflammatory roles. Loratadine, as a selective inverse-agonist of peripheral receptor H1, is described as an anti-allergic substance with potential antiinflammatory effects. We aimed to assess the protective capacity of loratadine against oxidative stress produced by inflammation with carrageenan in comparison with a well-known antioxidant compound, resveratrol.Our results showed that resveratrol and loratadine had no protective anti-inflammatory effects in inflamed skin. As expected, resveratrol had antioxidant effects in serum and in liver. Loratadine developed oxidative stress in tegument and serum.In this experimental model, our results do not sustain the initial hypothesis that loratadine could have a protective effect in inflammation, and, in the contrary, is capable of increasing it, by producing an oxidative stress.

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Inhibition of cytokine generation and mediator release by human basophils treated with desloratadine

Cited by 96 publications

References 26 publications

Desloratadine Inhibits Constitutive and Histamine-Stimulated Nuclear Factor-κB Activity Consistent with Inverse Agonism at the Histamine H<sub>1</sub> Receptor

Desloratadine Inhibits Constitutive and Histamine-Stimulated Nuclear Factor-κB Activity Consistent with Inverse Agonism at the Histamine H<sub>1</sub> Receptor

The H1 histamine receptor regulates allergic lung responses

Resveratrol and Loratadine Effects on Oxidative Stress Induced by Experimental Inflammation

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