Upregulation of interleukin 21 and promotion of interleukin 17 production in chronic or recurrent Vogt-Koyanagi-Harada disease

Arch Ophthalmol. 2010 Nov;128(11):1449-54. doi: 10.1001/archophthalmol.2010.265.

Abstract

Objectives: To analyze the expression and potential role of interleukin (IL) 21 in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.

Methods: Blood samples were obtained from patients with VKH disease and from healthy control subjects. Serum IL-21 level and IL-21 messenger RNA (mRNA) expression by peripheral blood mononuclear cells (PBMCs) were determined by enzyme-linked immunosorbent assay and by reverse transcriptase-polymerase chain reaction, respectively. Interleukin 17 and interferon γ levels in the supernatants of PBMCs and CD4(+) T cells cultured with anti-CD3 and anti-CD28 antibodies in the presence or absence of recombinant IL-21 were detected by enzyme-linked immunosorbent assay.

Results: The results showed a significantly increased serum IL-21 level, as well as higher IL-21 mRNA expression by PBMCs, in patients having chronic or recurrent active VKH disease compared with patients having inactive VKH disease and with controls. In vitro experiments showed that recombinant IL-21 significantly increased IL-17 production by PBMCs and by CD4(+) T cells from patients and from controls. However, recombinant IL-21 did not affect interferon γ expression by PBMCs or by CD4(+) T cells.

Conclusion: Interleukin 21 may be involved in the pathogenesis of chronic or recurrent VKH disease, possibly by promoting IL-17 secretion.

Clinical relevance: Findings from the present study suggest that IL-21 may be a potential target in the development of therapy for VKH disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Chronic Disease
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation / physiology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-17 / biosynthesis*
  • Interleukin-21
  • Interleukins / blood
  • Interleukins / genetics*
  • Interleukins / pharmacology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • RNA, Messenger / genetics
  • Recombinant Proteins / pharmacology
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uveomeningoencephalitic Syndrome / genetics*
  • Uveomeningoencephalitic Syndrome / metabolism

Substances

  • Interleukin-17
  • Interleukins
  • RNA, Messenger
  • Recombinant Proteins
  • Interferon-gamma
  • Interleukin-21