Full Papers
TNF-α inhibitors reduce inflammation-induced concentric remodelling, but not diastolic dysfunction in collagen-induced arthritis
R. Le Roux1, L. Mokotedi2, S. Fourie3, A. Manilall4, S. Gunter5, A.M. Millen6
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. aletta.millen@wits.ac.za
CER13991
2022 Vol.40, N°1
PI 0024, PF 0032
Full Papers
PMID: 33427610 [PubMed]
Received: 01/09/2020
Accepted : 14/12/2020
In Press: 11/01/2021
Published: 28/01/2022
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.
