Understanding the significance of cytokines and chemokines in the pathogenesis of alopecia areata

Exp Dermatol. 2020 Aug;29(8):726-732. doi: 10.1111/exd.14129. Epub 2020 Jul 3.


Alopecia areata has basically been understood as a type 1 inflammatory disease. Activated NKG2D+ CD8+ cells produce the Th1 cytokine interferon-γ, which leads to the disruption of immune tolerance of hair follicles and the exposure of self-antigens. This results in dense inflammatory cell infiltration and apoptosis around hair follicles, inducing hair loss. A well-known complication of alopecia areata is atopic dermatitis, a typical type 2 inflammatory disease. Hair scientists have shied away from confronting and understanding how alopecia areata, a type 1 inflammatory disease, and atopic dermatitis, a type 2 inflammatory disease, can occur together. This review summarizes the research on the cytokine balance in alopecia areata and then focuses on the classification of the cytokine balance in alopecia areata, including the classification of atopic dermatitis into extrinsic and intrinsic types. Dupilumab reportedly showed dual efficacy in a patient with concomitant atopic dermatitis and alopecia areata, supporting our own experience. Elevated Th2 cytokine levels have also been reported in patients with alopecia areata, with increased serum IL-4, IL-5, IL-6 levels, high IgE levels and elevated eosinophil levels. Because local immunotherapy is a treatment that induces Th2-type inflammation, it may worsen the condition of alopecia areata patients with extrinsic atopic dermatitis. It is desirable to select appropriate treatments with consideration of the cytokine balance.

Keywords: Th1; Th2; alopecia areata; atopic dermatitis; dupilumab.

Publication types

  • Review

MeSH terms

  • Alopecia Areata / immunology*
  • Alopecia Areata / metabolism*
  • Alopecia Areata / virology
  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Chemokines / metabolism
  • Cytokines / metabolism*
  • Dermatitis, Atopic / drug therapy
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / metabolism*
  • Dermatologic Agents / therapeutic use
  • Eosinophils
  • Humans
  • Immunoglobulin E / blood
  • Interleukin-4 / blood
  • Interleukin-5 / blood
  • Interleukin-6 / blood
  • Th2 Cells


  • Antibodies, Monoclonal, Humanized
  • Chemokines
  • Cytokines
  • Dermatologic Agents
  • IL4 protein, human
  • IL5 protein, human
  • IL6 protein, human
  • Interleukin-5
  • Interleukin-6
  • Interleukin-4
  • Immunoglobulin E
  • dupilumab