The role of IL-1 in the pathogenesis of heart disease.
ABSTRACT Interleukin (IL)-1 consists of two distinct ligands, IL-1alpha and IL-1beta, with indistinguishable biological activities that signal through the IL-1 type I receptor (IL-1RI). A naturally occurring IL-1 receptor antagonist (IL-1Ra) binds to IL-1RI without initiating signal transduction and prevents IL-1 signaling, competitively inhibiting IL-1-mediated responses. Emerging evidence suggests that the balance between IL-1 agonists and antagonists plays an essential role in a variety of cardiovascular conditions. IL-1 may play a role in atherothrombotic disease by promoting the formation of atheromatous lesions, enhancing vascular inflammation, and triggering plaque destabilization. Following myocardial infarction, IL-1 critically regulates the inflammatory response and is involved in the development of adverse remodeling by enhancing expression of matrix metalloproteinases. IL-1 signaling may also be an essential mediator in the pathogenesis of heart failure by suppressing cardiac contractility, promoting myocardial hypertrophy, and inducing cardiomyocyte apoptosis. The present review summarizes current available data showing the significant role of IL-1 signaling in heart disease and raising the possibility that IL-1 inhibitors (such as anakinra, a nonglycosylated recombinant human IL-1Ra) may be clinically useful agents in patients with certain cardiovascular conditions.
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ABSTRACT: We describe an enzyme-linked immunosorbent assay (ELISA) for antibodies to HTLV-I using synthetic peptides corresponding to antigenic regions of HTLV-I structural protein. We observed that the peptides amino acid 100-119, 100-130, 131-160 and 295-314 of the gag protein, and 89-115, 175-199, 350-386 and 458-488 on the env protein correspond to the antigenic regions of HTLV-I structural protein. In particular, the peptide corresponding to amino acid 100-130 of the gag protein reacted with antibodies in all sera from HTLV-I carriers diagnosed by particle agglutination assay (PA) and indirect immunofluorescence assay (IF), but did not react with sera from healthy volunteers judged to be negative by PA and IF. Our results indicate that the ELISA using the peptide 100-130 of the gag protein can be used for donor screening of HTLV-I antibodies.International Journal of Cancer 06/1990; 45(5):865-8. · 5.44 Impact Factor
Article: Interleukin-1 beta induces cardiac myocyte growth but inhibits cardiac fibroblast proliferation in culture.[show abstract] [hide abstract]
ABSTRACT: Interleukin-1 (IL-1), initially called "endogenous pyrogen," is primarily known as a mediator of inflammation. However, it also plays many other diverse physiologic roles including the stimulation and inhibition of both primary cells in culture and the interstitial and parenchymal cells of a number of organs including the heart. In the heart, IL-1 expression has traditionally been reported in situations where there is immunologic myocardial injury such as occurs during transplant rejection and congestive heart failure. For this reason, all of the effects of IL-1 have been presumed to be deleterious. Using a cell culture model which allows both the muscle cells (myocytes) and nonmuscle cells (fibroblasts) to be evaluated separately, we have found that IL-1 induces both cardiac myocyte hypertrophy and reinitiates myocyte DNA synthesis. In stark contrast, IL-1 exerts a potent anti-proliferative effect on cardiac fibroblasts. To our knowledge this is the first report concerning the differential effects of IL-1 on myocardial cell growth in culture and, given the inducible expression of IL-1 by myocardial cells during stress, underscores the importance of investigating the complex nature of the intracardiac cell-cell interactions that occur in the heart.Journal of Clinical Investigation 07/1995; 95(6):2555-64. · 15.39 Impact Factor
Article: Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling.[show abstract] [hide abstract]
ABSTRACT: Cardiac remodeling is generally accepted as a determinant of the clinical course of heart failure (HF). Defined as genome expression resulting in molecular, cellular and interstitial changes and manifested clinically as changes in size, shape and function of the heart resulting from cardiac load or injury, cardiac remodeling is influenced by hemodynamic load, neurohormonal activation and other factors still under investigation. Although patients with major remodeling demonstrate progressive worsening of cardiac function, slowing or reversing remodeling has only recently become a goal of HF therapy. Mechanisms other than remodeling can also influence the course of heart disease, and disease progression may occur in other ways in the absence of cardiac remodeling. Left ventricular end-diastolic and end-systolic volume and ejection fraction data provide support for the beneficial effects of therapeutic agents such as angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking agents on the remodeling process. These agents also provide benefits in terms of morbidity and mortality. Although measurement of ejection fraction can reliably guide initiation of treatment in HF, opinions differ regarding the value of ejection fraction data in guiding ongoing therapy. The role of echocardiography or radionuclide imaging in the management and monitoring of HF is as yet unclear. To fully appreciate the potential benefits of HF therapies, clinicians should understand the relationship between remodeling and HF progression. Their patients may then, in turn, acquire an improved understanding of their disease and the treatments they are given.Journal of the American College of Cardiology 04/2000; 35(3):569-82. · 14.16 Impact Factor