Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome

Fibroblast growth factor-21 (FGF21) is elevated in patients with the metabolic syndrome. Although the exact underlying mechanisms remain ill-defined, chronic low-grade inflammation with increased Interleukin-(IL)-1 beta expression may be responsible. The aim of this study was to investigate effects of two different anti-inflammatory treatments (IL-1 antagonism or high-dose corticosteroids) on FGF21 in patients with the metabolic syndrome. This is a secondary analysis of two interventional studies in patients with obesity and features of the metabolic syndrome. Trial A was an interventional trial (n=73) investigating short-term effects of the IL-1 antagonist anakinra and of dexamethasone. Trial B was a randomized, placebo-controlled, double-blinded trial (n=67) investigating longer-term effects of IL-1 antagonism. In total, 140 patients were included in both trials. Median age was 55 years (IQR 44-66), 26% were female and median BMI was 37 kg/m(2) (IQR 34-39). Almost half of the patients were diabetic (45%) and had increased c-reactive protein levels of 3.4 mg/L. FGF21 levels correlated with fasting glucose levels, HOMA-index, C-peptide levels, HbA1c and BMI. Short-term treatment with anakinra led to a reduction of FGF21 levels by - 200 pg/mL (95%CI - 334 to - 66; p=0.004). No effect was detectable after longer-term treatment (between-group difference: - 8.8 pg/mL (95%CI - 130.9 to 113.3; p=0.89). Acute treatment with dexamethasone was associated with reductions of FGF21 by -175 pg/mL (95%CI - 236 to - 113; p<0.001). Anti-inflammatory treatment with both, IL-1 antagonism and corticosteroids reduced FGF21 levels at short-term in individuals with the metabolic syndrome.Trial registration: ClinicalTrials.gov Identifiers NCT02672592 and NCT00757276.