Interleukin-31 pathway and its role in atopic dermatitis: a systematic review.
BACKGROUND
Atopic dermatitis, a chronic inflammatory disease, has a lifetime prevalence of 10-20%. Atopic dermatitis reduces quality of life, primarily due to pruritus. Interleukin-31 and its target receptor are newly discovered entities that are involved in pruritus.


OBJECTIVE
To summarize the current understanding of interleukin-31 and its role in atopic dermatitis, potential therapeutic interventions and future prospects.


METHODS
A systematic review was designed to identify articles related to interleukin-31 and its role in pruritus. Predefined queries containing interleukin-31 and related key terms were searched with no past date restriction, through 31 August 2016, using MEDLINE, Cochrane Controlled Trials Register, ClinicalTrials.gov and the International Clinical Trials Registry Platform Search Portal database.


RESULTS
Of 151 identified articles, 61 met eligibility criteria. Interleukin-31 receptors are expressed constitutively on the surface of keratinocytes, eosinophils and small diameter neurons. Overexpression of interleukin-31, independent of mast cells and lymphocytes, induces clinical and histological features consistent with atopic dermatitis. In addition, overexpression of interleukin-31 causes reversible alopecia. Human monoclonal interleukin-31 antagonist, CIM331, decreased pruritus in phase-I and phase-II clinical trials.


CONCLUSIONS
Interleukin-31 plays an important role in atopic dermatitis and alopecia. Inhibiting this pathway may provide an alternative to antihistamines for the pruritus of atopic dermatitis.
a Department of Dermatology , Wake Forest School of Medicine, Center for Dermatology Research , Winston-Salem , NC , USA.
Mohammed D
MD
Saleem
a Department of Dermatology , Wake Forest School of Medicine, Center for Dermatology Research , Winston-Salem , NC , USA.
Elias
E
Oussedik
a Department of Dermatology , Wake Forest School of Medicine, Center for Dermatology Research , Winston-Salem , NC , USA.
Veronica
V
D'Amber
a Department of Dermatology , Wake Forest School of Medicine, Center for Dermatology Research , Winston-Salem , NC , USA.|b Department of Pathology , Wake Forest School of Medicine , Winston-Salem , NC , USA.|c Department of Pathology and Public Health Sciences , Wake Forest School of Medicine , Winston-Salem , NC , USA.
Steven R
SR
Feldman
D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D004485:Eczema / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007378:Interleukins / Q000097:blood; D011537:Pruritus / Q000188:drug therapy / Q000473:pathology; D018123:Receptors, Interleukin / Q000276:immunology* / Q000378:metabolism
D018926:Anti-Allergic Agents; D061067:Antibodies, Monoclonal, Humanized; C502187:IL31 protein, human; C502188:IL31RA protein, human; D007378:Interleukins; D018123:Receptors, Interleukin; D007073:Immunoglobulin E; C000612881:nemolizumab
IL-31; cytokine; eczema; glycoprotein 130-like receptor; itch; mechanism; pathophysiology; pruritus; receptor structure; signal transduction; treatment