Etanercept downregulates the Th17 pathway and decreases the IL-17+/IL-10+ cell ratio in patients with psoriasis vulgaris

J Clin Immunol. 2012 Dec;32(6):1221-32. doi: 10.1007/s10875-012-9716-x. Epub 2012 Jun 15.

Abstract

Purpose: To evaluate circulating and lesional CD4(+) and CD8(+) cells belonging to Th1, Th2, and Th17 patterns as well as IL-10(+) cells before and after a 12-week lasting course with etanercept or acitretin in patients with psoriasis.

Methods: 15 patients were given etanercept 50 mg twice weekly and 15 patients acitretin 0,4 mg/kg/day, both for 12 weeks. At the baseline and at the end of the treatment, blood and skin samples were taken to investigate IL-4, IL-8, IL-10, IL-17, and IFN-γ-producing CD4(+) and CD8(+) cells. As controls, 10 healthy controls (HC) and 6 atopic dermatitis (AD) patients were included into the study.

Results: Psoriasis patients showed augmented IL-17- and IL-8-producing CD4(+) cells in the blood than HC and AD patients. In the skin lesions, IL-17(+) cells were more represented in psoriasis than in AD, while the number of IL-4-producing cells was reduced in psoriasis patients than in AD ones. Etanercept was able to significantly reduce the number of IL-17- and IL-8-producing CD4(+) and CD8(+) cells both in skin and blood, as well as to augment the proportion of IL-10-producing CD4(+) cells in the skin of psoriatic patients, while acitretin was not.

Conclusions: Our results confirmed the role of Th17 cells in the pathogenesis of psoriasis. Etanercept, but not acitretin, was able to downregulate the Th17 pathway and to increase the percentages of IL-10-producing cells in the skin.

MeSH terms

  • Acitretin / pharmacology
  • Acitretin / therapeutic use
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Dermatitis, Atopic / blood
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / pathology
  • Down-Regulation / drug effects
  • Drug Administration Schedule
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use*
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Keratolytic Agents / pharmacology
  • Keratolytic Agents / therapeutic use
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Psoriasis / blood
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Psoriasis / pathology
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Signal Transduction / drug effects*
  • Skin / drug effects
  • Skin / immunology
  • Skin / pathology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • IL10 protein, human
  • Immunoglobulin G
  • Interleukin-17
  • Keratolytic Agents
  • Receptors, Tumor Necrosis Factor
  • Interleukin-10
  • Acitretin
  • Etanercept