Abstract: Rheumatoid arthritis (RA) is the most common inflammatory musculoskeletal disease and an important cause of diminished quality-of-life for the affected individuals and with a major impact on society because of decreased work-force participation. Treatment of RA has been advanced dramatically during the past two decades by the advent of biological therapies. A large number of such agents have been approved and several additional ones are in late-stage clinical developments. Because of the high price of biologics, pharmacoeconomical considerations have become an important part of the appraisal of such medications. Current therapeutic developments include the development of additional biologics with various specific targets, the development of small-molecule compounds with similar efficacies, and entirely new approaches to treat autoimmune inflammatory diseases such as RA. ... Read more

Abstract: Why chronic inflammatory reactions persist in specific sites, such as rheumatoid arthritis in the joints, remains a mystery. Current models of inflammation have concentrated upon the responses of lymphocytes such as B and T cells to specific antigens, and have attempted, often unsuccessfully, to address the causative agent. However recent studies have shown that stromal cells such as macrophages, endothelial cells, and fibroblasts play important roles in the switch that turns a spontaneously resolving acute inflammatory response within a tissue into chronic and persistent disease. Therapeutic manipulation of the stromal microenvironment has been particularly effective in treating cancer and is likely to provide novel therapies to achieve improved control of chronic inflammatory disease. ... Read more

Abstract: Non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin and disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate have been the mainstay treatments for rheumatoid arthritis for decades. In the past few years, anti-TNF-α (tumor necrosis factor-α) biopharmaceuticals have sparked a revolution. More drugs targeting the inflammation pathway are in the works. ... Read more

Cells of the innate immune system, such as macrophages, NK cells, neutrophils, eosinophils and particularly dendritic cells (DC), guide immune reactivity towards a protective antitumor response, according to the cytokines that these cells are specialized to produce. The immunological linking of the adaptive immune response and innate immune system is orchestrated by cytokines like GM-CSF, TNF, IL-12, IL-18 and IFN-γ that are produced by the cells of the innate immune system in response to physiological cues of “danger.” These so-called “danger-signals” include tissue inflammation and destruction as well as soluble and secreted components of bacterial or fungal species and factors ... Read more

If you have been skeptical about targeting one molecule as a therapeutic means to treat a complex disease with unknown etiology, then you’ll be pleasantly surprised. Drugs that treat rheumatoid arthritis by targeting tumor necrosis factor a (TNF-α) are such examples. We know that inflammation causes the pathology of the disease. It is widely known that autoimmune responses lead to the avalanche of inflammatory responses in rheumatoid arthritis. But we know little for sure about what incited the autoimmune reactions. In addition, dozens of molecules are involved in distinct pathways in the inflammation process. TNF-α is an important factor but ... Read more

In a report by Wuest T. et al. (1) of the Institute of Biology and Immunology, University of Stuttgart, Germany, the hypothesis tested was that genetically engineering the tumor necrosis factor (TNF) prodrug would combine the desirable features of a drug with the necessary selective tumoricidal bioactivity without the detrimental systemic side effects. In a similar and equally innovative report by Van Molle et al. (2), it was shown that when mice are placed in a humid, 420C environment for 20 minutes, the systemic bioactivity of TNF is desirably altered. The result permits the tumoricidal properties of TNF while suppressing ... Read more