Author
Charles A. Dinarello
Other affiliations: University of Guadalajara, Pennsylvania State University, University of Colorado Boulder ...read more
Bio: Charles A. Dinarello is an academic researcher from University of Colorado Denver. The author has contributed to research in topics: Interleukin & Cytokine. The author has an hindex of 190, co-authored 1058 publications receiving 139668 citations. Previous affiliations of Charles A. Dinarello include University of Guadalajara & Pennsylvania State University.
Papers published on a yearly basis
Papers
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TL;DR: Results indicate that IL-1 may be an intrinsic neuromodulator in central nervous system pathways that mediate various metabolic functions of the acute phase reaction, including the body temperature changes that produce the febrile response.
Abstract: Interleukin-1 (IL-1) is a cytokine that mediates the acute phase reaction. Many of the actions of IL-1 involve direct effects on the central nervous system. However, IL-1 has not previously been identified as an intrinsic component within the brain, except in glial cells. An antiserum directed against human IL-1 beta was used to stain the human brain immunohistochemically for IL-1 beta-like immunoreactive neural elements. IL-1 beta-immunoreactive fibers were found innervating the key endocrine and autonomic cell groups that control the central components of the acute phase reaction. These results indicate that IL-1 may be an intrinsic neuromodulator in central nervous system pathways that mediate various metabolic functions of the acute phase reaction, including the body temperature changes that produce the febrile response.
759 citations
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TL;DR: It is demonstrated that human blood monocytes release processed IL-1beta after a one-time stimulation with either TLR2 or TLR4 ligands, resulting from constitutively activated caspase-1 and release of endogenous adenosine triphosphate.
733 citations
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TL;DR: IL-1ra reduces the severity of sepsis, colitis, arthritis and diabetes in animals and is presently being tested in humans with arthritis, shock and myelogenous leukemia.
725 citations
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TL;DR: A recent advance in the field has been that of differential cytokine production, which can be used to classify human disease as being “ autoimmune” or “autoinflammatory” thus impacting on therapeutic interventions.
Abstract: Cytokines affect nearly every biological process; these include embryonic development, disease pathogenesis, non-specific response to infection, specific response to antigen, changes in cognitive functions and progression of the degenerative processes of aging. In addition, cytokines are part of stem cell differentiation, vaccine efficacy and allograft rejection. This short insight focuses on the milestones in cytokine biology and how the various and often contradictory activities of these small, non-structural proteins affected the fields of inflammation and immunology. Multiple biological properties or pleiotropism is the hallmark of a cytokine. Today, the term "cytokine" encompasses interferons, the interleukins, the chemokine family, mesenchymal growth factors, the tumor necrosis factor family and adipokines. As of this writing, 33 cytokines are called interleukins, but many are part of families of related but distinct gene products. There are certainly over 100 separate genes coding for cytokine-like activities, many with overlapping functions and many still unexplored. Also discussed in this overview are the failures and successes of cytokines as therapeutic targets. A recent advance in the field has been that of differential cytokine production, which can be used to classify human disease as being "autoimmune" or "autoinflammatory" thus impacting on therapeutic interventions.
693 citations
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TL;DR: In this paper, the authors support a key role for cytokines in left ventricular remodeling in congestive heart failure (CHF) patients and show that elevated plasma cytokine levels are associated with increased mortality.
Abstract: Background— Experimental studies support a key role for cytokines in left ventricular remodeling. In congestive heart failure (CHF) patients, elevated plasma cytokine levels are associated with wor...
687 citations
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TL;DR: An American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference was held in Northbrook in August 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae as mentioned in this paper.
12,583 citations
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TL;DR: The ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.
Abstract: Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.
10,861 citations
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TL;DR: The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
Abstract: The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
9,282 citations
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Cooper University Hospital1, St George's Hospital2, Memorial Hospital of Rhode Island3, Emory University4, University of Colorado Denver5, McMaster University6, Washington University in St. Louis7, University of Chicago8, University of Jena9, Rush University Medical Center10, University of Pittsburgh11, University of Pennsylvania12, Federal University of São Paulo13, University of Toronto14, Royal Perth Hospital15, Guy's and St Thomas' NHS Foundation Trust16, Université libre de Bruxelles17
TL;DR: An update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008 is provided.
Abstract: Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke
9,137 citations
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TL;DR: The new appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework for understanding the clinical benefits of lipid-lowering therapies and unravelling the details of inflammatory pathways may eventually furnish new therapeutic targets.
Abstract: Abundant data link hypercholesterolaemia to atherogenesis. However, only recently have we appreciated that inflammatory mechanisms couple dyslipidaemia to atheroma formation. Leukocyte recruitment and expression of pro-inflammatory cytokines characterize early atherogenesis, and malfunction of inflammatory mediators mutes atheroma formation in mice. Moreover, inflammatory pathways promote thrombosis, a late and dreaded complication of atherosclerosis responsible for myocardial infarctions and most strokes. The new appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework for understanding the clinical benefits of lipid-lowering therapies. Identifying the triggers for inflammation and unravelling the details of inflammatory pathways may eventually furnish new therapeutic targets.
7,858 citations