Interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis.

Abstract

OBJECTIVE:

The aim of this study was to examine the pro-inflammatory effects of IL-6 in ex vivo temporal artery explant cultures.

METHODS:

Patients meeting 1990 ACR classification criteria for GCA were prospectively recruited. Temporal artery biopsies were obtained and temporal artery explants cultured ex vivo with IL-6 (10-40 ng/ml) in the presence or absence of its soluble receptor (sIL-6R; 20 ng/ml) for 24 h. Explant supernatants were harvested after 24 h and assayed for IFN-γ, TNF-α, Serum amyloid A, IL-1β, IL-17, IL-8, angiotensin II and VEGF by ELISA. Myofibroblast outgrowths, cytoskeletal rearrangement and wound repair assays were performed.

RESULTS:

IL-6 augmented production of VEGF, but not of any of the other pro-inflammatory mediators assayed. No differences were observed in the explants cultured in the presence or absence of the sIL-6R or between those with a positive (n = 11) or negative (n = 17) temporal artery biopsy. IL-6 did not enhance myofibroblast proliferation or migration. Western blot analysis confirmed signalling activation, with increased expression of pSTAT3 in response to IL-6+sIL-6R.

CONCLUSION:

IL-6 stimulation of temporal artery explants from patients with GCA neither increased expression of key pro-inflammatory mediators nor influenced myofibroblast proliferation or migration.

• Authors: Lorraine O'Neill, Jennifer McCormick, Wei Gao, Douglas J Veale, Geraldine M McCarthy, Conor C Murphy, Ursula Fearon, Eamonn S Molloy
• Journal: Rheumatology advances in practice (Rheumatol Adv Pract) Vol. 3 Issue 1 Pg. rkz011 ( 2019) ISSN: 2514-1775 [Electronic] England
• PMID: 31431999 (Publication Type: Journal Article)