Copyright © 2006, European Society of Cardiology
Interleukin-10 is not a critical regulator of infarct healing and left ventricular remodeling
Section of Cardiovascular Sciences, Baylor College of Medicine and the Methodist Hospital, One Baylor Plaza M/S F-602, Houston TX 77030, United States
* Corresponding author. Tel.: +1 713 798 4188; fax: +1 713 796 0015. Email address: ngf{at}bcm.tmc.edu
Objective: Interleukin-10 (IL-10) exerts potent anti-inflammatory actions and modulates matrix metalloproteinase expression. We hypothesized that endogenous IL-10 may regulate infarct healing and left ventricular remodeling by promoting resolution of the post-infarction inflammatory response and by modulating extracellular matrix metabolism.
Methods: IL-10 null and wildtype (WT) mice underwent reperfused infarction protocols. We compared the healing response and remodeling-associated parameters between IL-10 –/– and WT infarcts. In addition, we studied the effects of IL-10 on inflammatory gene synthesis by stimulated murine cardiac fibroblasts.
Results: Infarcted IL-10 –/– mice exhibited comparable mortality rates with WT animals. Although IL-10 –/– mice had higher peak tumor necrosis factor (TNF)-
and monocyte chemoattractant protein (MCP)-1/CCL2 mRNA levels in the infarcted heart than WT mice, both groups demonstrated timely repression of pro-inflammatory cytokine and chemokine mRNA synthesis after 24 h of reperfusion and exhibited a similar time course of resolution of the neutrophil infiltrate. IL-10 gene disruption did not alter fibrous tissue deposition and dilative remodeling of the infarcted heart. Pre-incubation with IL-10 did not modulate the pro-inflammatory phenotype of TNF--stimulated cardiac fibroblasts, failing to inhibit chemokine mRNA synthesis. In contrast, transforming growth factor (TGF)-β1 pre-incubation suppressed interferon-
-inducible protein (IP)-10/CXCL10 synthesis by cardiac fibroblasts exposed to TNF-.
Conclusions: IL-10 signaling plays a non-critical role in suppression of inflammatory mediators, resolution of the inflammatory response, and fibrous tissue deposition following myocardial infarction. This may be due to the relative selectivity of IL-10-mediated anti-inflammatory actions, with respect to cell type and stimulus. Resolution of post-infarction inflammation is likely to involve multiple overlapping regulatory mechanisms controlling various pro-inflammatory pathways activated in the infarcted myocardium.
KEYWORDS Cytokines; Hispathology; Infarction; Interleukins; Remodeling
Time for primary review 15 days
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