Interleukin-17 Inhibition for the Treatment of Inflammatory Skin Disease

  • Jason E. Hawkes
  • Jose A. Gonzalez
  • James G. Krueger
Chapter
First Online:

Abstract

Psoriasis is a chronic inflammatory skin condition characterized by thick, erythematous, scaly plaques. While the etiology of this skin condition has not been fully elucidated, research has unequivocally shown that psoriasis represents a bona fide T cell-mediated disease. The recent discovery of a set of pathogenic T cells that produce high levels of interleukin-17 in response to interleukin-23 led to a major paradigm shift in the pathogenic model for this condition. The astonishing phase III clinical trial results for three novel monoclonal antibodies against interleukin-17 (secukinumab, ixekizumab, and brodalumab) underscore the central role of this cytokine as the predominant driver of psoriatic disease. The role of interleukin-17 blockade for the treatment of other inflammatory skin conditions is not entirely clear, though early studies suggest that this class of medications represents a promising treatment strategy for several noninfectious lymphocytic and neutrophilic dermatoses, such as Sweet syndrome, Behçet disease, and atopic dermatitis.

Keywords

Interleukin-17 Interleukin-23 Secukinumab Ixekizumab Brodalumab Psoriasis Atopic dermatitis Lupus Neutrophilic dermatosis 

Abbreviations

ACR

American College of Rheumatology

AD

Atopic dermatitis

ADAMTSL5

A disintegrin-like and metalloprotease domain containing thrombospondin type 1 motif-like 5

AMPs

Antimicrobial peptides

C/EBP

CCAAT-enhancer-binding protein

DLE

Discoid lupus erythematosus

EAE

Experimental autoimmune encephalomyelitis

IBD

Inflammatory bowel disease

IL

Interleukin

ILC

Innate lymphoid cells

PASI

Psoriasis Area and Severity Index

SCLE

Subacute cutaneous lupus erythematosus

SLE

Systemic lupus erythematosus

STAT1

Signal transducer and activator of transcription 1

T17

Interleukin-17-producing T cells

Tc17

Interleukin-17-producing CD8+ T cells

Th

T helper

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Notes

Acknowledgments

JEH, JAG, and JGK are supported in part by grant # UL1TR001866 and # KL2TR001865 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program.

Conflict of Interest

JEH and JAG declare that they have no conflict of interest. JGK has been a consultant to and has received research support from companies that have developed or are developing therapeutics for psoriasis: AbbVie, Amgen, Boehringer, Bristol-Myers Squibb, Celgene, Dermira, Idera, Janssen, Leo, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, Serono, Sun, Valeant, and Vitae.

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Jason E. Hawkes
    • 1
  • Jose A. Gonzalez
    • 1
  • James G. Krueger
    • 1
  1. 1.The Laboratory for Investigative DermatologyThe Rockefeller UniversityNew YorkUSA

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