gastrin-releasing-peptide and Dermatitis--Atopic

Topics: Animals; Blotting, Western; Dermatitis, Atopic; Disease Models, Animal; Gastrin-Releasing Peptide; Humans; Immunohistochemistry; Interleukin-22; Interleukins; Keratinocytes; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pruritus; Real-Time Polymerase Chain Reaction; Signal Transduction; Skin

Despite recent insights into the pathophysiology of acute and chronic itch, chronic itch remains an often intractable condition. Among major contributors to chronic itch is dysfunction of spinal cord gamma aminobutyric acidergic (GABAergic) inhibitory controls.. We sought to test the hypothesis that selective GABA agonists as well as cell transplant-derived GABA are antipruritic against acute itch and in a transgenic mouse model of atopic dermatitis produced by overexpression of the T. We injected wild-type and IL-31Tg mice with combinations of GABA-A (muscimol) or GABA-B (baclofen) receptor agonists 15 to 20 minutes prior to injection of various pruritogens (histamine, chloroquine, or endothelin-1) and recorded spontaneous scratching before and after drug administration. We also tested the antipruritic properties of intraspinal transplantation of precursors of GABAergic interneurons in the IL-31Tg mice.. Systemic muscimol or baclofen are antipruritic against both histamine-dependent and -independent pruritogens, but the therapeutic window using either ligand alone was very small. In contrast, combined subthreshold doses of baclofen and muscimol produced a significant synergistic antipruritic effect, with no sedation. Finally, transplant-mediated long-term enhancement of GABAergic signaling not only reduced spontaneous scratching in the IL-31Tg mice but also dramatically resolved the associated skin lesions.. Although additional research is clearly needed, existing approved GABA agonists should be considered in the management of chronic itch, notably atopic dermatitis.

Topics: Animals; Antipruritics; Baclofen; Dermatitis, Atopic; Disease Models, Animal; Drug Synergism; GABA-A Receptor Agonists; GABA-B Receptor Agonists; Gastrin-Releasing Peptide; Glutamate Decarboxylase; Interleukins; Interneurons; Male; Median Eminence; Mice, Inbred C57BL; Mice, Transgenic; Muscimol; Receptors, Bombesin; Receptors, GABA-A; Receptors, GABA-B; Receptors, Neurokinin-1; RNA, Messenger; Skin; Spinal Cord; Stem Cell Transplantation

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H. This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients.. Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays.. Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD.. Plasma GzmB levels may reflect the degree of pruritus and dermatitis in patients with AD.

Topics: Adult; Case-Control Studies; Dermatitis; Dermatitis, Atopic; Enzyme-Linked Immunosorbent Assay; Female; Gastrin-Releasing Peptide; Gene Expression Regulation; Granzymes; Humans; Inflammation; Killer Cells, Natural; Male; Middle Aged; Pruritus; Psoriasis; T-Lymphocytes, Cytotoxic

Topics: Adolescent; Adult; Dermatitis, Atopic; Eczema; Female; Gastrin-Releasing Peptide; Humans; Male; Middle Aged; Pruritus; Young Adult

Topics: Adult; Dermatitis, Atopic; Female; Gastrin-Releasing Peptide; Humans; Male; Middle Aged; Pruritus; Young Adult

Topics: Animals; Dermatitis, Atopic; Disease Models, Animal; Gastrin-Releasing Peptide; Male; Mice; Mice, Mutant Strains; Nerve Fibers, Unmyelinated; Pruritus; Skin