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.

Interleukin-1 and the response to injury.

Abstract: Traumatic injury is the leading cause of morbidity and mortality in Americans less than 45 years old. People surviving the initial insult undergo metabolic, hemodynamic and immunologic changes which contribute to both early and late complications. Though necessary for normal immunologic response and for wound healing, pathologic alterations of IL-1 synthesis, degradation, and binding to receptors on both a local and systemic level could lead to these changes. Manipulation of IL-1-mediated effects might be of therapeutic utility in the management of trauma in the future.

Parasite-monocyte interactions in human leishmaniasis: production of interleukin-1 in vitro

Abstract: Leishmania are obligate intracellular protozoa that parasitize mononuclear phagocytes. Because mononuclear phagocytes are also the primary source of leukocytic pyrogen and of lymphocyte-activating factor, both considered properties of interleukin-1 (IL-1), we investigated in vitro production of leukocytic pyrogen and of lymphocyte-activating factor from human monocytes infected with Leishmania tropica. Despite parasitization of 95% of cells, 24- and 48-hr culture supernatants and cell lysates derived from L. tropica-infected monocytes did not contain IL-1. Leishmania that were killed by freezing or by glutaraldehyde treatment similarly did not induce monocyte production of IL-1. Of importance is the observation that human monocytes infected with L. tropica for 6 hr and then challenged with a potent IL-1 inducer (Staphylococcus epidermidis) produced significantly less IL-1 than did uninfected monocytes that were similarly challenged (P less than .001). This difference was not affected by the addition of indomethacin to the cultures. In contrast, soluble immune complexes prepared with an excess of L. tropica antigen and rabbit antibody to L. tropica induced high levels of IL-1 production from normal monocytes. Neither antigen nor antibody alone incubated with monocytes led to significant production of IL-1, however. Thus, these studies suggest that despite leishmanial adherence to, entrance into, and replication within human monocytes there is little or no stimulation of IL-1 production. This may represent a parasite evasion mechanism that retards the development of protective immune responses in leishmaniasis.

The pathogenesis of atherosclerosis: a perspective for the 1990s

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.

Cancer-related inflammation.

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.

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

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

Inflammation in atherosclerosis

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.