scispace - formally typeset
Search or ask a question
Author

Charles A. Dinarello

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
More filters
Journal Article
TL;DR: In this paper, the antipyretic effect of inhibitors of protein synthesis was studied in vitro under controlled conditions and the amount of prostaglandin E2 (PGE2) measured in the supernatant fluid was assayed by radioimmunoassay.
Abstract: In order to study the antipyretic effect of inhibitors of protein synthesis, hypothalamic tissue was incubated in vitro under controlled conditions and the amount of prostaglandin E2 (PGE2) measured in the supernatant medium. Rabbit anterior hypothalamic tissue was incubated with purified human leukocytic pyrogen (LP) and after 60 minutes the supernatant fluid was assayed for PGE2 by radioimmunoassay. Control tissue incubated with Eagle's medium (MEM) released elevated levels of PGE2; however, the addition of polymyxin B (PmxB), a cationic antibiotic which blocks the activities of bacterial endotoxins, significantly reduced PGE2. In addition, endotoxin added to MEM induced from the brain tissue PGE2 production which could be reduced by the addition of PmxB. Thus, commercial culture media such as MEM may contain sufficient amounts of endotoxin to stimulate brain PGE2 production in vitro. Purified human LP incubated with hypothalamic tissue in the presence of PmxB induced PGE2 production in a dose-dependent fashion. This release could be reduced (p less than 0.001) by the presence of either cycloheximide or puromycin during incubation with LP. The addition of these inhibitors to unstimulated hypothalamic tissue incubations did not reduce background levels of PGE2. It is concluded that the antipyretic effect of protein synthesis inhibitors results in a specific decrease in LP-induced levels of PGE2.

12 citations

Journal ArticleDOI
TL;DR: It is found that the antibody anti-IL-1 beta inhibits mitogen stimulated lymphocyte DNA synthesis in dose-dependent concentrations and is most probably due to the inhibition of endogenous IL-1, which is a very important signal for T cell activation.

12 citations

Patent
10 Aug 2012
TL;DR: In this article, the authors describe compositions and methods for treatment of conditions associated with bone marrow transplantations in a subject, for example, Graft versus host Disease (GvHD) or Bone marrow transplantation rejection.
Abstract: Embodiments of the present invention relate to compositions and methods for treatment of subjects in need of or having a bone marrow transplant. Certain embodiments describe compositions and methods for treatment of conditions associated with bone marrow transplantations in a subject, for example, Graft versus Host Disease (GvHD) or bone marrow transplantation rejection. Some embodiments concern early or immediate bone marrow transplantation rejection. Certain embodiments relate to compositions and uses of alpha1-antitrypsin (α1-antitrypsin, AAT) and carboxyterminal peptide derivatives thereof and/or compositions and uses of serine protease inhibitors, immunomodulators or anti-inflammatory agent activity similar to that of AAT.

12 citations

Journal ArticleDOI
27 Sep 2012-Blood
TL;DR: It is reported that mild heating of mice enhances the postradiation recovery of neutrophils via an IL-1, IL-17, and G-CSF mechanism, indicating that Interleukin-1 is a master cytokine regulating inflammatory and immune responses.

12 citations

Journal ArticleDOI
TL;DR: This study reports that recombinant IL-18 primes resting mouse spleen-derived NKcells to transduce effective signals, which allows IL-2 to trigger proliferation and survival of NK cells, and reveals the anti-inflammatory properties of IL- 18.
Abstract: Most immune related studies on IL-18 have focused on its property to induce IFN-γ . Indeed, Haruki Okamura and coworkers described in 1995 the release of a cytokine from Propionibacterium acnes-primed liver macrophages stimulated with LPS and gave the cytokine the name “IFN-γ inducing factor”.1 In this issue of the Journal, El-Darawish reports that recombinant IL-18 primes resting mouse spleen-derived NKcells to transduce effective signals, which allows IL-2 to trigger proliferation and survival of NK cells.2 Themain point of their study is that IL-18 is the driver of signal transduction via PI3/AKT, mTOR, ATG, and LC3 in NK cells. IL-18 primed NK cells respond to IL-2 and increase CD25 expression. Using IL-18 deficientmouseNK cells, there is no significant expansion. There is considerable clinical importance to IL-18 in the context of NK cells survival. As described below in this commentary, IL-18 activation of NK cells is consistent with the pathogenesis of the hemophagocytic lymphohistiocytosis syndrome and the related macrophageactivation syndrome.However, in their SignificanceStatement, the authors state “The concept that IL-18 is merely an IFN-γinducer limited research of IL-18 roles in other cellular processes”. We disagreewith this view that research on IL-18was limited to the induction of IFN-γ . On the contrary, research on IL-18 has been studied extensively during the last 20 years in models of human disease and cellular activation quite independent of IFN-γ . The early studies of IL-18 focused on its similarities with IL-1β because the precursor forms of both cytokines require caspase-1 cleavage to convert to active cytokines. However, IL-18 is hardly a recapitulation of IL-1β . The precursor of IL-18 is present constitutively in epithelial cells of the skin, liver, gastrointestinal tract, and kidney of healthy humans and healthy mice, whereas IL-1β is not constitutive in health and is not found in epithelial cells.3 Recent interest in IL-18 comes from missense mutations in NLRP3 where loss of control of caspase-1 cleavage results in a large spectrum of inflammatory diseases termed “autoinflammatory”. In general, manifestations of autoinflammatory diseases are independent of T-cells and IFN-γ . Mice deficient in IL-18 spontaneously develop metabolic syndrome while eating a standard mouse diet. This study and several others reveal the anti-inflammatory properties of IL-18 as reviewed in Ref. 3. IL-18 also plays a significant a role in myocardial suppression, heart failure, and atherosclerosis.3 In heart failure, it is difficult to envision a role for IFN-γ .4 Figure1 lists properties of IL-18,which are independent aswell as related to IFN-γ .3

12 citations


Cited by
More filters
Journal ArticleDOI
01 Jun 1992-Chest
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

Journal ArticleDOI
29 Apr 1993-Nature
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

Journal ArticleDOI
24 Jul 2008-Nature
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

Journal ArticleDOI
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

Journal ArticleDOI
19 Dec 2002-Nature
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