Detection and localization of cytokine immunoreactivity in retro-ocular connective tissue in Graves' ophthalmopathy

A. E. Heufelder, R. S. Bahn

Research output: Contribution to journalArticle

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Abstract

Paracrine interactions between fibroblasts residing in the retro-ocular space and infiltrating lymphocytes/macrophages are thought to be of central importance in the pathogenesis of Graves' ophthalmopathy (GO). Although various roles have been suggested for interferon-γ (IFNγ), tumour necrosis factor-α (TNα) and interleukin-1α (IL-1α) in GO, their actual presence in Graves' retro-ocular connective tissue has not been demonstrated. We examined surgical specimens obtained during orbital decompression from patients with severe GO (n = 6), and from normal individuals (n = 5), for the presence of IFNγ, TNFα and IL-1α. We used immunohistochemical methods on frozen tissue sections and primary fibroblast cultures, and sodium dodecylsulfate polyacrylamide-gel electrophoresis of tissue extracts and tissue culture supernatants. In addition, immunohistochemical staining of tissues for characterization of the mononuclear infiltrates was performed. Aggregates of mononuclear cells in retro-ocular connective and fatty tissue were found in five of six GO tissue specimens, but in none of the control specimens. We detected immunoreactivity for the three cytokines (IFNγ, TNFα and IL-1α) in the five GO tissue specimens that contained mononuclear cell aggregates. In addition, IL-1α immunoreactivity was demonstrable in primary and subsequent GO fibroblast cultures and in their supernatants. In contrast, no immunoreactivity for any of these cytokines was detected in tissue specimens, primary cultures or culture supernatants derived from normal individuals. The presence of mononuclear cell infiltrates and associated immunoreactivity for IFNγ, TNFα, IL-1α in retro-ocular connective tissue derived from patients with GO suggests that the previously demonstrated in vitro functions of these cytokines may indeed be operative in vivo. Our results further support the concept that IFNγ, TNFα and IL-1α may play a role in the pathogenesis of GO.

Original languageEnglish (US)
Pages (from-to)10-17
Number of pages8
JournalEuropean Journal of Clinical Investigation
Volume23
Issue number1
StatePublished - 1993

Fingerprint

Graves Ophthalmopathy
Connective Tissue
Interleukin-1
Tissue
Cytokines
Interferons
Fibroblasts
Cell culture
Tissue culture
Tissue Extracts
Lymphocytes
Macrophages
Frozen Sections
Decompression
Electrophoresis
Adipose Tissue
Polyacrylamide Gel Electrophoresis
Tumor Necrosis Factor-alpha
Sodium
Staining and Labeling

Keywords

  • Connective tissue
  • Graves' ophthalmopathy
  • Interferon-γ
  • Interleukin-1α
  • Mononuclear cells
  • Tumour necrosis factor-α

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Detection and localization of cytokine immunoreactivity in retro-ocular connective tissue in Graves' ophthalmopathy. / Heufelder, A. E.; Bahn, R. S.

In: European Journal of Clinical Investigation, Vol. 23, No. 1, 1993, p. 10-17.

Research output: Contribution to journalArticle

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