https://journal.chestnet.org/article/S0012-3692(16)38415-X/pdf

Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis

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.

The pathogenesis of atherosclerosis: a perspective for the 1990s

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.

/pdf/cancer-related-inflammation-ltml0xgfd3.pdf

Cancer-related inflammation.

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

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

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.

Inflammation in atherosclerosis

IL:32: A new pro-inflammatory cytokine involved in HCV-related liver inflammation and fibrosis

A Comparison of Neutralizing and Antigen-Binding Assays for Human Antibodies Against Toxic-Shock-Syndrome Toxin I

163 : Recombinant IL-37 inhibits LPS induced inflammation in a SIGIRR- and MAPK-dependent manner

Background NLRP3 is an essential component of the inflammasome, an intracellular macromolecular complex, which activates caspase-1 for the processing and release of active IL-1β and IL-18. Activation of the NLRP3 inflammasome takes place in inflammatory joint diseases, including gout. Although inhibition of IL-1β with either the IL-1 receptor antagonist anakinra or canakinumab, a neutralizing monoclonal antibody for IL-1β is highly effective for reducing the gout flares, a clinical need remains for a safe, oral treatment of recurrent gout flares refractory to standard of care. The small orally active and safe β-sulfonyl nitrile molecule OLT1177 is a specific inhibitor of the NLRP3 inflammasome, and currently being evaluated in a Phase 2 study for the treatment of acute gout flares. Objectives To investigate the anti-inflammatory effect of NLRP3 inflammasome inhibitor OLT1177 in mouse models of acute joint inflammation. Methods Two models of experimental arthritis were used in mice: zymosan- and monosodium urate (MSU)-induced arthritis. Knee joints of male C57BL/6 mice were injected intraarticularly with 180 μg heat-killed Zymosan or 300 μg of monosodium urate (MSU) crystals mixed with 200 μM C16.0 fatty acid and bovine serum albumin. Joints were assessed 24 and 4 hours after the zymosan or MSU/C16.0 injection, respectively, for clinical, histological and cytokine analyses. Results Intraarticular Zymosan induced a severe joint swelling with neutrophil infiltration, high levels of synovial IL-1β, IL-6 and the neutrophil chemokine CXCL1. Treatment with OLT1177 induced reduction of joint swelling and neutrophil infiltration (P Conclusions The orally active molecule OLT1177 is a potent inhibitor of IL-1β-driven inflammatory arthritis, particularly in a model of acute gout. Considering the outstanding safety profile in humans, OLT1177 is a potential therapeutic strategy to target NLRP3-driven IL-1β-mediated disorders. Disclosure of Interest C. Marchetti: None declared, B. Swartzwelter: None declared, M. Koenders: None declared, C. Dinarello Grant/research support from: Charles A. Dinarello serves on the Scientific Advisory Board of Olatec and receive compensation, L. Joosten Grant/research support from: Leo A. B. Joosten serves on the Scientific Advisory Board of Olatec and receive compensation

https://ard.bmj.com/content/annrheumdis/76/Suppl_2/89.2.full.pdf

Charles A. Dinarello

Papers

IL:32: A new pro-inflammatory cytokine involved in HCV-related liver inflammation and fibrosis

A Comparison of Neutralizing and Antigen-Binding Assays for Human Antibodies Against Toxic-Shock-Syndrome Toxin I

163 : Recombinant IL-37 inhibits LPS induced inflammation in a SIGIRR- and MAPK-dependent manner

OP0090 The human safe NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of experimental arthritis

Interleukin-2 production is suppressed by dietary N-3 fatty acids but enhanced by oral aspirin.