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

Actions of endotoxin, interleukin-I and tumor-necrosis-factor on arachidonic-acid metabolism in human amnion cells

Embodiments of the present invention illustrate methods of treating and preventing transplantation and side effects associated with transplantation. In particular, the present invention relates to compositions and methods for inhibition of graft rejection and promotion of graft survival. Thus, the invention relates to modulation of cellular activities, including graft rejection, promotion of graft survival, graft versus host rejection and conditions commonly associated with graft rejection. More particularly, the present invention relates to the inhibitory compounds comprising naturally occurring and man-made inhibitors of serine protease and inducers of other alpha1-antitrypsin activities.

Compositions and methods related to graft versus host disease and treatments thereof

Allo-Antigen Expression on Both APCS and Tumor Is Required To Elicit an Effective GVL Response after Experimental Allogeneic BMT.

Objective. To determine the effects of rheumatoid arthritis (RA) on whole-body protein metabolism. Methods. We examined protein metabolism and its hormonal and cytokine mediators before and 12 weeks after progressive resistance muscle strength training in 8 healthy young (mean k SD age 25 2 2 years) and 8 healthy elderly (70 rt 5 years) men and women, and in 8 adults with RA (42 2 13 years). An additional 6 healthy elderly subjects (69 k 3 years) served as a swimming-only control group. Results. Subjects with RA had higher rates of protein breakdown than did young or elderly healthy subjects (79.9 f 17.2 versus 60.3 f 5.8 and 63.7 2 12.4 pmoles/gm total body potassium/hour, respectively, P < 0.05), while there was no effect of age per se. Patients treated with methotrexate had normal rates of protein breakdown (P < 0.01 versus RA without methotrexate; P not significant versus healthy young subjects). Increased protein catabolism in RA was no longer evident

Effects of Muscle Strength Training and Tumor Necrosis Factor a

Interleukin (IL)-38 is the latest discovered member of the interleukin-1 family, which has anti-inflammatory properties similar to IL-36Ra. Several studies compared circulating IL-38 concentrations in healthy and diseased populations to characterize its role in both auto-immune and inflammatory pathologies, with both higher and lower concentrations being associated with certain diseases. However, in order to use IL-38 as a biomarker, a reference range in healthy adults is needed. To establish a reference IL-38 circulating concentration, accessible data from 25 eligible studies with IL-38 concentrations in healthy adults was collected. To validate the values found in literature, we measured IL-38 concentrations by enzyme-linked immunosorbent assay (ELISA) in several cohorts from our own institute. Additionally, the effect of blood collection techniques, freeze thawing cycles, and hemolysis on IL-38 measurements was assessed. To evaluate the importance of the genetic background of individuals as confounding factor of IL-38 synthesis, we used publicly available eQTL databases with matched data on allele frequencies in individuals of different ethnicities. Mean IL-38 concentrations in the various studies were weighted by their corresponding sample size, resulting in a weighted mean, and weighted upper and lower limits were calculated by mean ± 2 SD. Differences of over 10.000-fold were found in the weighted means between studies, which could not be attributed to the blood collection method or assessment of IL-38 in plasma or serum. Although IL-38 concentrations were markedly higher in Chinese then in European population studies, we could not show an association with the genetic background. From our analysis, a reference range for circulating IL-38 in healthy adults could thus not yet be established.

Charles A. Dinarello

Papers

Actions of endotoxin, interleukin-I and tumor-necrosis-factor on arachidonic-acid metabolism in human amnion cells

Compositions and methods related to graft versus host disease and treatments thereof

Allo-Antigen Expression on Both APCS and Tumor Is Required To Elicit an Effective GVL Response after Experimental Allogeneic BMT.

Effects of Muscle Strength Training and Tumor Necrosis Factor a

Circulating interleukin-38 concentrations in healthy adults