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.

Compositions for regulation of tumor necrosis factor-alpha

Abstract: The present invention relates to compositions and methods relating to an interleukin18-inducible cytokine termed tumor necrosis factor-alpha inducing factor (TAIF) or interleukin-32 (IL-32). In particular, the present invention provides compositions and methods for treating autoimmune diseases and cancer, in part by regulation of tumor necrosis factor-alpha expression.

Phorbol myristate acetate-protein complex mimics bioactivity of human IL-1. 1. Direct evidence that PMA temporarily enters and is released from cellular compartment during superinduction protocol.

Abstract: The K-562 cell line was treated with the superinduction protocol involving phorbol myristate acetate (PMA) for production of human interleukin 1 (IL-1). The resultant dialyzed K-562 superinduced supernatants contained potent IL-1-like activity when tested in 4 bioassays for IL-1. However, these K-562 SIS failed to induce fever in rabbits, the IL-1 like activity was not inhibited by an anti-human IL-1 antiserum in the murine thymocyte (LAF) assay, and the IL-1-like activity did not adhere to a specific immunoadsorbent column. Together with recent evidence that PMA may contaminate supernatants produced by the superinduction protocol and can mimic IL-1 bioactivity (9,10), the results of these novel methods suggested that IL-1 was not the bioactive moiety in K-562 SIS. To further examine the source of K-562 SIS IL-1-like activity, the active K-562 SIS were fractionated over Sephadex G-50, and the large molecular weight component (approximately 50,000) was found to express potent LAF activity yet remained nonpyrogenic. 3H-PMA was added to the superinduction protocol as a tracer for PMA migration. The 3H-PMA provided new and direct evidence that PMA adhered to or entered K-562 cells and adhered to plastic culture flasks during the serum free wash steps of the superinduction, and that PMA was released by K-562 cells into the serum containing supernatants during the incubation phase of the protocol. A 3H-PMA component of K-562 SIS co-migrated on gel filtration with the large molecular weight proteins which expressed LAF activity, and is a nondialyzable contaminant of superinduction supernatants. This PMA/protein complex is the main and perhaps the sole mediator of four distinct biological activities ascribed to IL-1.

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.