Expression of tumor necrosis factor-alpha protein in the myocardium in fatal myocarditis

Background: Tumor necrosis factor (TNF)-alpha is the most studied cytokine in the failing human heart and in experimental murine myocarditis. We have investigated the expression of TNF-alpha in the myocardium in human myocard itis. Methods: We examined endomyocardial biopsy (n = 4) and autopsy (n = 5) tiss ues obtained from nine patients diagnosed with myocarditis by the Dallas cr iteria. Expression of TNF-alpha in the hearts was immunohistochemically stu died using monoclonal antibodies against human TNF-alpha. Results: Tumor necrosis factor-alpha protein was expressed in the myocardiu m of six of the nine patients studied. Four of five fatal patients showed i ntense immunoreactivity for TNF-alpha compared with survivors. Furthermore, left ventricular systolic function was reduced in patients with TNF-alpha- positive hearts. Conclusions: These findings may support the suggestion that TNF-alpha plays an important role in cardiac dysfunction and myocytic damage in fatal huma n myocarditis.