Immune modulation: role of the inflammatory cytokine cascade in the failing human heart.
Recent studies have determined that expression of inflammatory mediators, such as cytokines and chemokines, is an important factor in the development and progression of heart failure (HF). These inflammatory mediators are expressed in response to various myocardial insults, including myocardial ischemia, viral infection, and toxins, and appear to have a detrimental effect on cardiac function and prognosis in HF patients. Our previous reports have shown activation of inflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), in the myocardium and peripheral monocytes in patients with HF. Indeed, sustained increases in cytokines, including TNF-alpha and its receptor, lead to monocyte phenotype transition, myocytic apoptosis, and activation of matrix metalloproteinase. This in turn modifies the interstitial matrix, augmenting further ventricular remodeling. Thus, in view of the emerging importance of TNF-alpha in the pathogenesis of HF, we review the effects of TNF-alpha on the physiology of the heart and the development of clinical strategies to target the inflammatory cytokine cascade.
Satoh
Mamoru
M
Department of Internal Medicine II and Memorial Heart Center, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan. m_satoh@imu.ncvc.go.jp
Minami
Yoshitaka
Y
Takahashi
Yuji
Y
Nakamura
Motoyuki
M