Proinflammatory cytokine genes are constitutively overexpressed in the heart in experimental systemic lupus erythematosus: A brief communication

Michiyo Tomita, Monica Dragoman, Heath Worcester, Philip Conran, Thomas J. Santoro

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The heart is one of a number of organs that may be affected in systemic lupus erythematosus (SLE), a prototypic autoimmune disease. Potential anatomical sites of involvement include the myocardium, pericardium, endocardium, valves, conduction system and blood vessels that subserve the heart. Typically, the severity of cardiovascular disease in lupus correlates with the degree of systemic inflammation, which is mirrored by the level of C-reactive protein (CRP) in the plasma. C-reactive protein, in turn is regulated by proinflammatory cytokines, such as interleukins (ILs) 1β and 6. These cytokines have been found in functionally and/or structurally damaged areas of the heart and have been implicated in disease pathogenesis. It has been assumed that the source of these putatively pathogenetically relevant cytokines in the compromised heart is infiltrating mononuclear cells. This study tests the hypothesis that cardiomyocytes per se may contribute to proinflammatory cytokine production in the setting of systemic inflammation. Using as the experimental model MRL/MpJ-Tnfrs6lpr (MRL-lpr/ lpr) mice, which spontaneously manifest an autoimmune syndrome that has clinical features of SLE, we show that ventricular homogenates and ventricular cardiomyocytes constitutively overexpress genes encoding the proinflammatory cytokines IL-1β, IL-6, IL-10, and gamma interferon. The results suggest the possibility that proinflammatory cytokines emanating from the heart may actually contribute to the high levels of CRP that appear to aid in predicting subsequent cardiac events. Viewed in this setting, CRP becomes a footprint of an ongoing pathogenic process mediated, in part, by the heart muscle itself.

Original languageEnglish (US)
Pages (from-to)971-976
Number of pages6
JournalExperimental Biology and Medicine
Volume229
Issue number9
DOIs
StatePublished - Oct 2004

Keywords

  • Atherosclerosis
  • Autoimmunity
  • Coronary heart disease
  • MRL-lpr/lpr mice
  • Proinflammatory cytokines
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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