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

Rheumatol Adv Pract. 2019 May 6;3(1):rkz011. doi: 10.1093/rap/rkz011. eCollection 2019.


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.

Keywords: giant cell arteritis; interleukin-6; temporal artery culture; tocilizumab.