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
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TL;DR: It is demonstrated that IL-38 suppresses spontaneous and stimulated osteogenic activity in aortic valve via inhibition of the NLRP3 inflammasome and caspase-1 and the findings suggest thatIL-38 has therapeutic potential for prevention of CAVD progression.
Abstract: Significance Calcific aortic valve disease (CAVD) is a common aging-related cardiovascular disease with no pharmacological therapy presently. CAVD pathobiology has chronic inflammation and progressive calcification in aortic valve leaflets. We found that aortic valve interstitial cells (AVICs) from CAVD valves have lower levels of the anti-inflammatory protein IL-38. Recombinant IL-38 reduces spontaneous calcium deposition in AVICs, as well as calcium deposition in AVICs from non-CAVD valves when subjected to pro-inflammatory stimulation. Mechanistically, IL-38 inhibits the NLRP3 inflammasome and suppresses the inflammatory and osteogenic activities in AVICs. Aged IL-38–deficient mice display aortic valve calcification when fed a high-fat diet. Thus, IL-38 suppresses inflammation to alleviate calcification in the aortic valve and may have therapeutic potential for prevention of CAVD progression.
4 citations
4 citations
TL;DR: It is suggested that there is a therapeutic benefit of single doses of rhIL-11 in reducing LPS-induced IL-1β and TNFα production.
Abstract: To determine whether a single injection of recombinant human interleukin-11 (rhIL-11) to human subjects would affect endotoxin-inducible cytokine production, 6 dialysis-dependent patients with renal failure and 4 healthy volunteers were subcutaneously injected with rhIL-11 (50 µg/kg). The circulating concentrations of rhIL-11 remained at a constant level of approximately 12 ng/ml for 0.25—6 h in healthy volunteers but were 2-fold higher in dialysis-dependent patients. Venous blood obtained before and after rhIL-11 was stimulated with 10 ng/ml of LPS for 24 h at 37°C and production of TNFα, IL-1β, and IL-8 determined. The maximum suppression of IL-1β, TNFα and IL-8 production (66%, 24% and 58%, respectively) was observed 1 h after rhIL-11 administration. After 24 h, when circulating concentration of rhIL-11 had decreased to near pre-injection levels, LPS-induced TNFα and IL-1β production remained suppressed (56 ± 17%, P < 0.05; 46 ± 4.7, P<0.01, respectively) but returned to baseline at 48 h. These finding...
4 citations
4 citations
Journal Article•
TL;DR: Activation of the NLRP3 inflammasome during acute myocardial infarction mediates further inflammatory injury after reperfusion and this finding is consistent with previous work on the role of “cell reprograming” in inflammation.
Abstract: Introduction: Activation of the NLRP3 inflammasome during acute myocardial infarction (AMI) mediates further inflammatory injury after reperfusion. Several NLRP3 inflammasome inhibitors have been s...
3 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
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
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
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
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