TNF-alpha inhibitors reduce inflammation-induced concentric remodelling, but not diastolic dysfunction in collagen-induced arthritis

Objective To determine biologic disease-modifying anti-rheumatic drug effects on inflammation-induced cardiac geometry and function changes. Methods Male and female Sprague-Dawley rats (n=92) were divided into four groups: control group, collagen-induced arthritis (CIA) group, anti-TNF-alpha group and anti-IL-6 group. Inflammation was induced by injecting bovine type-II collagen emulsified in incomplete Freund's adjuvant at the base of the tail, in all groups except the control group. Following the onset of arthritis, the anti-TNF-alpha group received etanercept, and the anti-IL-6 group received tocilizumab, for six weeks. Left ventricular (LV) geometry and function were assessed with echocardiography and circulating inflammatory markers were measured with ELISA. Results Relative wall thickness in the CIA and anti-IL-6 groups were increased compared to controls (p<0.001 and p=0.02, respectively). TNF-alpha inhibition protected against inflammation-induced LV concentric remodelling, as relative wall thickness in the anti-TNF-alpha group was similar to controls (p=0.55). Systolic function variables were not different between the groups. In all groups inoculated with collagen, myocardial relaxation (lateral e') were impaired compared to controls (all p<0.001). LV filling pressures (E/e') were increased in the CIA, anti-TNF-alpha and anti-IL-6 groups compared to controls (p<0.001, p<0.001 and p=0.05, respectively). Independent of concentric remodelling, circulating CRP concentrations were associated with decreased e' and increased E/e', while TNF-alpha concentrations were associated with E/A. Conclusion TNF-alpha inhibition protected against inflammation-induced adverse cardiac remodelling, but not diastolic dysfunction. IL-6 receptors blocker effects on inflammation-induced cardiac changes were inconclusive. Systemic inflammation likely impacts LV concentric remodelling and diastolic dysfunction through distinct pathways.