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(Circulation. 1997;95:551-552.)
© 1997 American Heart Association, Inc.

Articles

Cytokines Score a Knockout

Harnessing Gene Targeting to Gain Insight Into the Pathogenesis of Myocarditis

Peter Libby, MD; Richard N. Mitchell, MD, PhD

the Departments of Medicine and Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave, Boston, Mass.

Correspondence to Peter Libby, MD, Vascular Medicine and Atherosclerosis Unit, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA 02115. E-mail plibby@bustoff.bwh.harvard.edu.

Key Words: Editorials • interleukins • lymphocytes • molecular biology • myocarditis

	Introduction

 
Circumstantial evidence implicates a number of cytokines, protein mediators of inflammation and immunity, in the pathogenesis of cardiovascular diseases ranging from heart failure to atherosclerosis. One such cytokine, tumor necrosis factor- (TNF-), has attracted considerable interest in this regard. The original descriptions of TNF- focused on its antitumor actions in mice primed with endotoxin¹ or as a mediator of cachexia in parasitically infected animals.² Although it was originally considered a product of macrophages, we now recognize that many cells can produce TNF-. In the context of cardiovascular biology, cardiac myocytes³ and vascular smooth muscle cells⁴ constitute potentially important sources of this multipotent mediator.

TNF may contribute to the pathogenesis of cardiovascular diseases in several ways. Although its effects on specific cells differ, TNF- generally elicits a spectrum of proinflammatory functions on target cells that may account for aspects of the pathological findings (Table). For example, in septic shock, augmented endothelial procoagulant activity and increased production of plasminogen activator inhibitor can promote disseminated intravascular coagulation and its consequences, including purpura fulminans and the Waterhouse-Friderichsen syndrome. TNF-induced augmentation in leukocyte adherence to microvascular endothelium can promote vascular plugging and may contribute to such clinical scenarios as reperfusion injury or adult respiratory distress syndrome in septic patients.

View this table: [in this window] [in a new window]   Table 1. Typical Actions of Tumor Necrosis Factor- on Target Cells

In congestive heart failure, the development of cardiac cachexia correlates with elevations in the circulating levels of TNF-.⁵ This cytokine can augment expression of nitric oxide synthetase and hence vasodilatation and . . . [Full Text of this Article]

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