Regulatory effects of antihistamines on the responses to staphylococcal enterotoxin B of human monocyte-derived dendritic cells and CD4+ T cells

Iida, Hideyuki; Asada, Hideo; Yokoi, Shoko; Niizeki, Hironori; Yasuda, Yasuki; Miyagawa, Sachiko; Kita, Eisuke

doi:10.1016/j.jdermsci.2008.04.004

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…CCL17 has been reported to be involved in cutaneous disease such as atopic dermatitis [36,37], and CCL22 has also been reported to associate with atopic dermatitis [38]. In human peripheral blood CD4 + T cells, the non‐sedative H1‐antagonist epinastine suppresses CCL17 expression [39,40]. This inhibitory effect of epinastine may be partially responsible for its attenuating effect on allergic diseases.…”

Section: Immunomodulatory Effects Of H1‐receptor Antagonistsmentioning

confidence: 99%

Histamine H1-receptor antagonists with immunomodulating activities: potential use for modulating T helper type 1 (Th1)/Th2 cytokine imbalance and inflammatory responses in allergic diseases

Okamoto

Iwata

Ohnuma

et al. 2009

Clinical and Experimental Immunology

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SummaryBeing a first-line treatment for hypersensitivity allergic disease, histamine H1-receptor antagonists possess anti-inflammatory activity in addition to being H1-receptor antagonists. While it is not purely a histamine-related condition, hypersensitivity allergic disease is associated with an increase in the number of T helper type 2 (Th2) cells and Th2 cytokines, and a decrease in the number of Th1 cells and Th1 cytokines. Suppression of Th2-type cytokine production in addition to H1-receptor blockade may therefore represent a successful therapeutic strategy for the treatment of hypersensitivity allergic diseases. H1-receptor antagonists have been reported to modulate immune cascade at various points by acting on T cell-related inflammatory molecules, including adhesion molecules, chemokines and inflammatory cytokines. These effects of H1-receptor antagonists may be optimized for the treatment of allergic diseases. Besides their ability to regulate inflammatory molecules, some H1-receptor antagonists have been reported to downregulate Th2 cytokine production. In particular, it has been shown that several H1-receptor antagonists specifically inhibit the production of Th2, but not Th1, cytokines. Accumulating evidence indicates a crucial role for Th1/Th2 cytokine imbalance on the development of allergic diseases. Accordingly, the use of H1-receptor antagonist with Th2 cytokine inhibitory activity to modulate Th1/Th2 cytokine imbalance might be a favourable strategy for the treatment of hypersensitivity allergic diseases. Furthermore, the identification of H1-receptor antagonists which possess immunoregulatory activities in addition to their anti-histamine activity will provide an important insight into the development of novel immunoregulatory drugs.

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Section: Immunomodulatory Effects Of H1‐receptor Antagonistsmentioning

confidence: 99%

Histamine H1-receptor antagonists with immunomodulating activities: potential use for modulating T helper type 1 (Th1)/Th2 cytokine imbalance and inflammatory responses in allergic diseases

Okamoto

Iwata

Ohnuma

et al. 2009

Clinical and Experimental Immunology

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“…The clinical effects of these agents are generally believed to be mediated by their antagonistic action against histamine. On the other hand, there is much evidence that antihistamines, such as azelastine hydrochloride (AZE), fexofenadine hydrochloride (FEX), ketotifen fumarate salt (KET) and oxatomide (OXA), inhibit inflammatory cytokine production by T cells in vitro and in vivo [1,2,3]. It was also observed that second-generation antihistamines, such as epinastine hydrochloride and FEX, suppressed production of the eosinophil chemoattractants RANTES and eotaxin by nasal fibroblasts in vitro [4,5].…”

Section: Introductionmentioning

confidence: 99%

Effect of Histamine H<sub>1</sub> Receptor Antagonists on TARC/CCL17 and MDC/CCL22 Production from CD14+ Cells Induced by Antigenic Stimulation in vitro

Shoji

Asano²,

Furuta³

et al. 2010

Int Arch Allergy Immunol

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Background: Thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) are accepted to be important molecules in the development and maintenance of allergic diseases. Although several types of histamine H₁ receptor antagonist (antihistamine) have been developed and used for the treatment of allergic diseases, the influence of antihistamines on TARC and MDC production is not well understood. Objective: The present study was undertaken to examine the influence of antihistamines on TARC and MDC production from CD14+ cells after antigenic stimulation in vitro. Methods: CD14+ cells prepared from patients with pollinosis to Japanese cedar pollen were stimulated with specific allergen extracted from Japanese cedar pollen (Cry j 1) in the presence of azelastine (AZE), ketotifen (KET), fexofenadine (FEX) and oxatomide (OXA) for 6 days. TARC and MDC levels in culture supernatants were examined by ELISA. We also examined the influence of FEX on TARC and MDC mRNA expression, phosphorylation of mitogen-activated protein kinases (MAPKs) and transcription factor activation in CD14+ cells after Cry j 1 stimulation. Results: FEX at 250 ng/ml, which is almost equal to therapeutic blood levels, caused a significant inhibition of TARC and MDC production.However, AZE, OXA and KET required higher concentrations than their therapeutic blood levels to suppress production of these factors. FEX at 250 ng/ml also suppressed NF-ĸB activation, phosphorylation of p38 MAPK and extracellular signal-regulated kinases 1 and 2 and expression of mRNA for TARC and MDC. Conclusions: These results suggest that antihistamines, especially FEX, suppress CC chemokine production from CD14+ cells through interference with antigen-mediated signaling and result in favorable modification of allergic disease states or conditions.

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“…Besides the effects of OLP on KC and LC, another study has shown that antihistamines regulate immune responses by affecting the interaction between DC and CD4 + T cells. 20 In summary, OLP suppresses the production of CCL17 by KC and DC. This suggests that OLP may exerts its therapeutic effect at least partly by downmodulating Th2 chemokine production by epidermal cells.…”

mentioning

confidence: 94%

“…OLP downregulated both CCL17 and CCL22 production by BMDC. Besides the effects of OLP on KC and LC, another study has shown that antihistamines regulate immune responses by affecting the interaction between DC and CD4 + T cells 20 …”

mentioning

confidence: 99%

Antihistaminic drug olopatadine downmodulates CCL17/TARC production by keratinocytes and Langerhans cells

Sugita

Miwa

Mori

et al. 2009

The Journal of Dermatology

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Regulatory effects of antihistamines on the responses to staphylococcal enterotoxin B of human monocyte-derived dendritic cells and CD4+ T cells

Cited by 4 publications

References 42 publications

Histamine H1-receptor antagonists with immunomodulating activities: potential use for modulating T helper type 1 (Th1)/Th2 cytokine imbalance and inflammatory responses in allergic diseases

Histamine H1-receptor antagonists with immunomodulating activities: potential use for modulating T helper type 1 (Th1)/Th2 cytokine imbalance and inflammatory responses in allergic diseases

Effect of Histamine H<sub>1</sub> Receptor Antagonists on TARC/CCL17 and MDC/CCL22 Production from CD14+ Cells Induced by Antigenic Stimulation in vitro

Antihistaminic drug olopatadine downmodulates CCL17/TARC production by keratinocytes and Langerhans cells

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