Antihistamines in the Treatment of Atopic Dermatitis

Herman, Stephen J.; Vender, Ronald

doi:10.1007/s10227-003-0164-3

Cited by 37 publications

(12 citation statements)

References 42 publications

(47 reference statements)

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“…Trimeprazine is a first-generation tricyclic antihistamine containing the same tricyclic core as phenothiazine antipsychotics such as chlorpromazine; however, it is used mainly as an antihistamine, an antipruritic, a sedative, or an antiemetic (24–26). Trimeprazine is best known as an H1R antagonist, but it can behave as a partial agonist (see below).…”

Section: Resultsmentioning

confidence: 99%

Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice

Kuznetsova

Hollister-Lock

et al. 2016

JCI Insight

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The capacity of pancreatic β cells to maintain glucose homeostasis during chronic physiologic and immunologic stress is important for cellular and metabolic homeostasis. Insulin receptor substrate 2 (IRS2) is a regulated adapter protein that links the insulin and IGF1 receptors to downstream signaling cascades. Since strategies to maintain or increase IRS2 expression can promote β cell growth, function, and survival, we conducted a screen to find small molecules that can increase IRS2 mRNA in isolated human pancreatic islets. We identified 77 compounds, including 15 that contained a tricyclic core. To establish the efficacy of our approach, one of the tricyclic compounds, trimeprazine tartrate, was investigated in isolated human islets and in mouse models. Trimeprazine is a first-generation antihistamine that acts as a partial agonist against the histamine H1 receptor (H1R) and other GPCRs, some of which are expressed on human islets. Trimeprazine promoted CREB phosphorylation and increased the concentration of IRS2 in islets. IRS2 was required for trimeprazine to increase nuclear Pdx1, islet mass, β cell replication and function, and glucose tolerance in mice. Moreover, trimeprazine synergized with anti-CD3 Abs to reduce the progression of diabetes in NOD mice. Finally, it increased the function of human islet transplants in streptozotocin-induced (STZ-induced) diabetic mice. Thus, trimeprazine, its analogs, or possibly other compounds that increase IRS2 in islets and β cells without adverse systemic effects might provide mechanism-based strategies to prevent the progression of diabetes.

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Section: Resultsmentioning

confidence: 99%

Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice

Kuznetsova

Hollister-Lock

et al. 2016

JCI Insight

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“…Hydrocortisone also displayed strong inhibitory activity on the production of cytokines and chemokines (Figures 2(a) and 2(b)), as reported previously [40], indicating that the experimental conditions were well established. To test whether CA can diminish itching of the skin based on histamine release [41], CA was examined using mast cells stimulated with anti-DNP-IgE. As seen in Figure 3, anti-DNP-IgE treatment stimulated the release of histamine up to 20-fold as assessed by measuring β -hexosaminidase activity [42].…”

Section: Resultsmentioning

confidence: 99%

Syk/Src Pathway-Targeted Inhibition of Skin Inflammatory Responses by Carnosic Acid

Choi

et al. 2012

Mediators of Inflammation

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Carnosic acid (CA) is a diterpene compound exhibiting antioxidative, anticancer, anti-angiogenic, anti-inflammatory, anti-metabolic disorder, and hepatoprotective and neuroprotective activities. In this study, the effect of CA on various skin inflammatory responses and its inhibitory mechanism were examined. CA strongly suppressed the production of IL-6, IL-8, and MCP-1 from keratinocyte HaCaT cells stimulated with sodium lauryl sulfate (SLS) and retinoic acid (RA). In addition, CA blocked the release of nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin E2 (PGE2) from RAW264.7 cells activated by the toll-like receptor (TLR)-2 ligands, Gram-positive bacterium-derived peptidoglycan (PGN) and pam3CSK, and the TLR4 ligand, Gram-negative bacterium-derived lipopolysaccharide (LPS). CA arrested the growth of dermatitis-inducing Gram-positive and Gram-negative microorganisms such Propionibacterium acnes, Pseudomonas aeruginosa, and Staphylococcus aureus. CA also blocked the nuclear translocation of nuclear factor (NF)-κB and its upstream signaling including Syk/Src, phosphoinositide 3-kinase (PI3K), Akt, inhibitor of κBα (IκBα) kinase (IKK), and IκBα for NF-κB activation. Kinase assays revealed that Syk could be direct enzymatic target of CA in its anti-inflammatory action. Therefore, our data strongly suggest the potential of CA as an anti-inflammatory drug against skin inflammatory responses with Src/NF-κB inhibitory properties.

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“…This might be surprising at first sight, as in general itch in atopic dermatitis patients is hardly ever reduced by antihistamines. It has to be mentioned as a possible explanation for their frequent use that 54.7% of patients suffered from concomitant rhinoconjunctivitis or other allergies [33,34,35]. …”

Section: Discussionmentioning

confidence: 99%

Therapeutic Benefits in Atopic Dermatitis Care from the Patients' Perspective: Results of the German National Health Care Study ‘Atopic Health'

Steinke

Langenbruch²,

Ständer³

et al. 2014

Dermatology

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Background/Aims: Numerous therapies are recommended to treat atopic dermatitis. The German national health care study ‘Atopic Health' generated nationwide data on the care situation from the patients' perspective. Methods: Data for 1,678 adult patients were collected within a retrospective cohort study throughout the year 2010. Six scores to capture satisfaction with care, quality of life (Dermatology Life Quality Index, EQ-5D-VAS), therapeutic success and benefits (Patient Benefit Index) were analyzed using descriptive methods and analysis of variance. Results: 82.1% of patients were highly satisfied with their treatment. Topical corticosteroids and climate therapies were associated with the best success ratings. Quality of life was moderately impaired (mean Dermatology Life Quality Index 8.5 ± 6.5). 88.4% of the patients indicated a relevant therapeutic benefit (Patient Benefit Index ≥1) with significantly better scores for topical immunomodulating therapies and climate therapies. Conclusion: The most frequently applied therapies presented pleasant success and benefit ratings, even if quality of life could be improved for more than one third of patients.

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Antihistamines in the Treatment of Atopic Dermatitis

Abstract: Dermatologists require additional evidence regarding the efficacy of antihistamines and their mechanism of action in the treatment of AD to enhance patient care.

Cited by 37 publications

References 42 publications

Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice

Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice

Syk/Src Pathway-Targeted Inhibition of Skin Inflammatory Responses by Carnosic Acid

Therapeutic Benefits in Atopic Dermatitis Care from the Patients' Perspective: Results of the German National Health Care Study ‘Atopic Health'

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