Interleukin-18: A Mediator of Inflammation and Angiogenesis in Rheumatoid Arthritis

Interleukin-18 (IL-18) is a highly regulated inflammatory cytokine that is elevated in synovial tissues and synovial fluids of patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis (OA) and patients with other arthropathies. Within the RA joint, IL-18 can contribute to the inflammatory process by inducing leukocyte extravasation through upregulation of endothelial cell adhesion molecules, the release of chemokines from RA synovial fibroblasts, and directly as a monocytes, lymphocyte, and neutrophil chemoattractant. IL-18 can also help maintain and develop the inflammatory pannus by inducing endothelial cell migration and angiogenesis. IL-18 does this directly by binding and activating endothelial cells and indirectly by inducing RA synovial fibroblasts to produce angiogenic chemokines and vascular endothelial growth factor. IL-18 is present in RA synovial fluid in high levels, where it functions as an angiogenic mediator and leukocyte chemoattractant. IL-18 mediates all these inflammatory processes by binding to its receptor, IL-18 receptor, and initiating the activation of different signaling cascades leading to changes in target cells gene expression and behavior. IL-18 has been identified as a potential therapeutic target in the treatment of RA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90485/1/jir-2E2011-2E0050.pd

Generalised scaling at subleading order

We study operators in the sl(2) sector of N=4 SYM in the generalised scaling limit, where the spin is large and the length of the operator scales with the logarithm of the spin. At leading order in the large spin expansion the scaling dimension at strong coupling is given in terms of the free energy of the O(6) model. We investigate the first subleading corrections to the scaling dimension and find that these too can be derived from the O(6) model in the strong coupling limit.Comment: 19 pages, v2: Equation corrected and references added, v3: references added, published versio

Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies (including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our  understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA