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

Regina Le Roux, Lebogang Mokotedi, Serena Fourie, Ashmeetha Manilall, Sule Gunter, Aletta Millen*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)


To determine biologic disease-modifying anti-rheumatic drug effects on inflammation-induced cardiac geometry and function changes.

Male and female Sprague-Dawley rats (n=92) were divided into four groups: control group, collagen-induced arthritis (CIA) group, anti-TNF-α 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-α 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.

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-α inhibition protected against inflammation-induced LV concentric remodelling, as relative wall thickness in the anti-TNF-α 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-α 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-α concentrations were associated with E/A.

TNF-α 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.
Original languageEnglish
Article number33427610
Pages (from-to)24-32
Number of pages9
JournalClinical Experimental Rheumatology
Issue number1
Publication statusPublished - 28 Jan 2022
Externally publishedYes


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