Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents - Current Issue

Tumor necrosis factor (TNF) is the prototype member of a large family of cytokines that plays a crucial role in metazoan biology. Recent advances have identified TNF-like cytokines and their cognate receptors as critical mediators of many inflammatory diseases. The field of TNF biology is ever-expanding, with over 60,000 citations listed in the Pubmed, highlighting the progress of the field and its significance to human health in Read More

Tumor necrosis factor (TNFα) is a pleiotropic cytokine that mediates diverse biological responses. In the immune system, TNFα facilitates many aspects of immune responses against pathogenic challenges. While TNFα plays a critical role in the immune defense against pathogens, hyper-activation of the TNFα signaling cascade often results in the development of inflammatory and autoimmune diseases. Examination of na Read More

NF-κB/Rel transcription factors are well-known for their roles in the regulation of inflammation and immunity. NF-κB also blocks programmed cell death (PCD) or apoptosis triggered by proinflammatory cytokine, tumor necrosis factor (TNF)α. Through transcriptional induction of distinct subsets of cyto-protective target genes, NF-κB inhibits the execution of apoptosis activated by this cytokine. This protective action is mediated, i Read More

Tumor necrosis factor receptor associated periodic syndrome (TRAPS) is a hereditary auto-inflammatory periodic fever syndrome associated with autosomal dominant ectodomain mutations in the 55kDa tumor necrosis factor receptor (TNFRSF1A). Over forty mutations in TNFRSF1A are associated with TRAPS. Plasma levels of soluble TNFRSF1A (sTNFRSF1A) are abnormally low in TRAPS patients, as is shedding of TNFRSF Read More

In the last ten years, blockade of the cytokine TNF-alpha has emerged as a powerful new treatment for Rheumatoid Arthritis and related inflammatory disorders. However, differences in efficacy and side effect profiles amongst TNF antagonists have revealed important differences in their mechanisms of action. In addition, TNF is only one of more than nineteen related cytokines in the TNF superfamily, each of which p Read More

Apoptotic cell death can be triggered by death-inducing cytokines such and TNFα, Fas Ligand, and TRAIL, and death-receptors TNF-Rs, Fas, and TRAIL-Rs, or by mitochondrial-sensed events. The biochemical signalling pathways that lead from death receptors or mitochondria to the degradation of DNA and apoptotic cell death are wellcharacterized. Furthermore, it is clear that apoptotic cell death is important for the Read More

The white adipose tissue (WAT) represents the most important structure of the organism able to provide energy stores and heat insulation. Recently, its has been postulated that the adipose tissue can be considered as a complex, essential, and highly active metabolic and endocrine organ. Indeed, it is able to respond to different signals from the endocrine organs and from the nervous the immune systems. More rec Read More

The nervous system and the immune system regulate a variety of essential, co-ordinated responses. Multiple anatomical and physiological connections exist between the CNS and the immune system and communication between these systems is relayed by multiple chemical messengers, ranging from small molecules such as nitric oxide to neuroendocrine peptides such as alpha melanocyte stimulating hormo Read More

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors with key metabolic roles in adipose tissue, liver and skeletal muscle. They are also expressed at significant levels in polymorphonuclear cells, monocyte/ macrophages, dendritic cells, T cells and B cells, suggesting that they may have a role in modulating the immune response. To date, evidence for such a role comes from numerous stud Read More

Histamine is a biogenic amine with a broad spectrum of activities in various physiological and pathological situations. Besides its well-characterised effects in allergic responses and in acute inflammation, histamine modulates the cytokine network, influencing T helper 1 and T helper 2 balance, and antibody isotype. In multiple sclerosis (MS), and its animal model of experimental autoimmune encephalomyelitis (EAE), there are s Read More

Vitamin D receptor (VDR) agonists are well-known for their capacity to control calcium metabolism and to regulate growth and differentiation of many cell types. More recently, it has become clear that VDR agonists possess exquisite immunoregulatory properties, mostly by targeting dendritic cells and T cells. These properties have been exploited in the treatment of several Th1-mediated experimental autoimmune di Read More