Current Drug Targets - Inflammation & Allergy - Volume 3, Issue 1, 2004

The balance between polymorphonuclear leukocytes (PMNL) apoptosis and necrosis in inflamed tissues is an important determinant of the degree of tissue injury. To prevent senescent PMNL from releasing their toxic contents into surrounding tissues, these cells become apoptotic and are then internalized by tissue macrophages. PMNL apoptosis and subsequent ingestion by macrophages are the major mechanisms for clearing Read More

In the last decades several preclinical models for sepsis have been used to study the pathophysiologic processes during sepsis. Although these studies revealed promising immunomodulating agents for the treatment of sepsis, clinical trials evaluating the efficacy of these new agents in septic patients were disappointing. It should be realized that most of the preclinical models for sepsis lack a localized infectious source fr Read More

Considerable amount of work has been done in the area of enzymatic and nonenzymatic oxidation of arachidonic acid. This effort resulted in understanding of the functions of lipid mediators - eicosanoids in various aspects of health and disease. A mechanism by which aspirin exerts therapeutic effects puzzled pharmacologists for a long time until John Vane, in 1971, discovered that aspirin and its congeners block for Read More

In the last decade, the understanding of the molecular mechanisms of regulation of the inflammatory process in chronic inflammatory diseases has moved remarkably forward. Recent evidence in various fields has consistently indicated that Tcells play a key role in initiating and perpetuating inflammation, not only via the production of soluble mediators but also via cell / cell contact interactions with a variety of cell types thro Read More

The use of non-steroidal anti-inflammatory drugs (NSAIDs) is frequently associated with serious adverse effects related to the inhibition of cyclooxygenase (COX) in tissues where prostanoids exert physiological effects, such as gastric mucosal defence, renal homeostasis and platelet aggregation. The discovery of a second COX isoform (COX-2) specifically induced in pathological tissues led to the development of select Read More

Chronic hepatitis B virus (HBV) infection is a well-recognized risk factor for the development of hepatocellular carcinoma (HCC), which is becoming a more prevalent clinical problem, especially in HBV-endemic areas. It is estimated that 1.25 million people in the United States and more than 300 million people worldwide are chronically infected with HBV. Despite the introduction of universal vaccination against hepatitis B in over 1 Read More

Non-steroid anti-inflammatory drugs (NSAIDs) are major drugs used in the treatment of inflammation and pain in a wide variety of disorders. NSAIDs constitute a diverse group of chemicals, categorized according to their chemical structures that share the same therapeutic properties. Among the main compounds are aspirin and salicylate, diclofenac and flurbiprofen. The best-known mechanism of action of NSAIDs is th Read More

Human innate immunity can respond to diverse microbial products, as well as other substances such as heat shock proteins, taxol, and unsaturated fatty acids. Mediated largely by a family of Toll-like-receptors (TLR) and associated intracellular downstream signaling molecules, human innate immune response serves multiple functions ranging from providing the first line of defense to coordinating cellular growth as well as oth Read More

The complement system is a key component of innate immunity, acting to protect the host from micro-organisms such as bacteria and other “foreign” threats, including tumor cells. However, excessive activation of complement can injure the host and can even be life threatening. These toxic effects are caused primarily by the excessive production of the anaphylatoxins C3a and C5a during complement activation and exc Read More

Estrogen appears to play a central role in the immune response and immunemediated diseases. Estrogen receptors are expressed in a variety of immunocompetent cells, including CD4+ and CD8+ T cells and macrophages. Clinical observations indicate that some autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, frequently remit during pregnancy but exacerbate, or have their onset during the postpar Read More

Thrombin is well known in its function as the ultimate serine protease in the coagulation cascade. Emerging evidence indicates that thrombin also functions as a potent signaling molecule that regulates physiologic and pathogenic responses alike in a large variety of cell populations and tissues. Accompanying CNS injury and other cerebral vascular damages, prothrombin activation and leakage of active thrombin into CNS parenc Read More