Prostaglandins and acute inflammatory reactions : studies on rat platelets and carrageenin-induced paw edema

Despite the vast amount of accumulated data on inflammation, there are still large gaps in our knowledge about the pathways involved in the development of an inflammatory response (see Ebert & Grant, 1974). Thus, effective therapy of several chronic inflarmnatory diseases is, at this moment, beyond medical capabilities. For the control of the inconvenient and painful symptoms of diseases like rheumatoid arthritis, physicians still have to rely on drugs which have largely been developed empirically and are used in an empirical way (eg. Kaye & Pemberton, 1976). The mode of action of several of these "anti-inflammatory drugs", Hhich often only relieve anoying symptoms of the disease, has for a long time been shrouded in mystery. Only recently, Vane and co-Harkers (1971) discovered the main biochemical action of a group of these drugs, kno.vn as non-steroidal anti-inflammatory drugs (NSAIDs), of which aspirin (acetylsalicylic acid) is the most familiar representative. It appeared that aspirin-like drugs suppress prostaglandin (PG) biosynthesis, both in vitro and in vivo (82,233,254). This led to the concept that inhibition of PG release explains the anti-inflammatory effect of NSAIDs

Dendritic Cells in Human Atherosclerosis: From Circulation to Atherosclerotic Plaques

Background. Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory infiltrates predominantly consisting of monocytes/macrophages and activated T cells. More recent is the implication of dendritic cells (DCs) in the disease. Since DCs were demonstrated in human arteries in 1995, numerous studies in humans suggest a role for these professional antigen-presenting cells in atherosclerosis. Aim. This paper focuses on the observations made in blood and arteries of patients with atherosclerosis. In principal, flow cytometric analyses show that circulating myeloid (m) and plasmacytoid (p) DCs are diminished in coronary artery disease, while immunohistochemical studies describe increased intimal DC counts with evolving plaque stages. Moreover, mDCs and pDCs appear to behave differently in atherosclerosis. Yet, the origin of plaque DCs and their relationship with blood DCs are unknown. Therefore, several explanations for the observed changes are postulated. In addition, the technical challenges and discrepancies in the research field are discussed. Future. Future studies in humans, in combination with experimental animal studies will unravel mechanisms leading to altered blood and plaque DCs in atherosclerosis. As DCs are crucial for inducing but also dampening immune responses, understanding their life cycle, trafficking and function in atherosclerosis will determine potential use of DCs in antiatherogenic therapies