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

Abstract

OBJECTIVES:

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-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.

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-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.

CONCLUSIONS:

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.

• Authors: Regina Le Roux, Lebogang Mokotedi, Serena Fourie, Ashmeetha Manilall, Sulè Gunter, Aletta M E Millen
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) Vol. 40 Issue 1 Pg. 24-32 (01 2022) ISSN: 0392-856X [Print] Italy
• PMID: 33427610 (Publication Type: Journal Article)

Chemical References

• Tumor Necrosis Factor Inhibitors
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Arthritis, Experimental (diagnostic imaging, drug therapy)
• Cattle
• Female
• Inflammation (drug therapy)
• Male
• Rats
• Rats, Sprague-Dawley
• Tumor Necrosis Factor Inhibitors
• Tumor Necrosis Factor-alpha
• Ventricular Dysfunction, Left (chemically induced, diagnostic imaging, drug therapy)