Drug therapy of heart failure: an immunologic view.

Heart failure (HF) is a clinical syndrome manifested by signs and symptoms of low cardiac output, pulmonary, and/or systemic congestion. Immunologically, HF is defined as a state of immune activation and persistent inflammation, especially the circulatory levels of inflammatory cytokines have been found to increase. Traditional drugs used in HF have expressed immunomodulatory and/or anticytokine activities that may participate in their therapeutic efficacy in the disease. The angiotensin-converting enzyme inhibitors like captopril and enalapril as well as the angiotensin II receptor antagonist losartan indicated in HF exerted reducing effects on the inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 at experimental and clinical levels. Aldosterone antagonists like spironolactone when administered concomitantly with losartan can attenuate angiotensin II-enhanced cytokine production in HF. Carvedilol beta-adrenergic blockers showed a wider spectrum of anti-inflammatory/anticytokine activity that proved to be associated with improvement of cardiac function and ejection fraction in patients with HF. The poor prognosis in HF despite the long experience with its treatment necessitated thinking about new drugs to be added to the traditional ones. Methotrexate and statins are examples of these drugs, especially because they exert immunologic effects. A low dose of methotrexate has been considered as a hopeful adjunct therapy in chronic HF, but large long-term clinical trials are required. Statins showed conflicting results, although they might be useful early after acute ischemic events associated with left ventricular dysfunction or failure, especially in younger patients with less advanced HF.