Silent arterial inflammation during the apparent remission state of Takayasu's arteritis. What do cytokines tell us?

OBJECTIVES: To evaluate serum cytokines as biomarkers of smoldering disease activity in patients with Takayasu's arteritis (TAK) in remission.

METHODS: Thirty-four TAK patients with stable disease during the last 6 months and 22 healthy controls (HC) were included in a cross-sectional study. Serum levels of pro-inflammatory, anti-inflammatory, Th1, Th2, Th9, Th17 and Th22 cytokines were measured by the multiplex technique.

RESULTS: No significant differences regarding serum cytokine levels were found between TAK patients and HC. Serum TNF-α, IL-17F, IL-21 and IL-23 were higher in patients presenting angiographic type V than in those presenting other angiographic types. Serum IL-17E, IL-17F, IL-22 and IL-23 were higher in TAK patients with previous ischaemic events compared with those without previous ischaemia. No differences in serum cytokines were observed between TAK patients with and without aneurysmal disease in the aorta or among TAK patients without therapy, those under immunosuppressive agents and patients on biological therapy. Independent associations were found regarding angiographic type V and higher serum levels of IL-4, IL-6, IL17A, IL-17E, IL-17F, IL-21, IL-22 and IL-23. Previous ischaemic events were independently associated with higher serum IL-4, IL-17E, IL-22 and IL-23. Daily prednisone dose had an inverse association with lower serum IL-4, IL6, IL-17A, IL-17E, IL-22 and IL-23. The simultaneous use of immunosuppressive and biological agents led to lower serum IL-4, IL-17E and IL-23 levels.

CONCLUSIONS: A smoldering inflammatory response with predominantly cytokines involved in Th17 response seems to be ongoing in TAK patients in remission with extensive disease or with previous ischaemic events.