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ANEMIAS AND OTHER RED CELL DISORDERS - PART 3

Cytokine viêm làm gián đoạn erythropoiesis thông qua hiệu ứng bổ sung cho những hepcidin và quá trình trao đổi chất sắt. IL-6 trực tiếp ngăn chặn erythropoietin sản xuất, tạo ra tình trạng thiếu hồng cầu tương đối cho một mức độ nhất định anemia.25 cytokine viêm khác có thể góp phần để sản xuất erythropoietin đàn áp cũng. | 66 OVERVIEW OF ANEMIA SECTION I Inflammatory cytokines disrupt erythropoiesis through effects additional to those on hepcidin and iron metabolism. IL-6 directly suppresses erythropoietin production creating a state of relative erythropoietin deficiency for a given degree of anemia.25 Other inflammatory cytokines likely contribute to suppressed erythropoietin production as well. At the distal end of the erythropoietic pathway inflammatory cytokines suppress erythropoietin responsiveness of hematopoietic precursor cells. IL-1 -Ỉ IFN-y and TNF-V play very prominent roles in this respect. When added to in vitro cultures of erythropoietic precursors IFN-y promotes apoptosis of these cells in direct opposition to erythropoietin activity.26 Other cytokines including TNF-V directly amplify this detrimental effect on hematopoiesis.27 This pernicious result of inflammatory cytokines is compounded by a shortening in the half-life of circulating red cells. The anemia induced by inflammatory cells is therefore multifactorial in origin. Reactive oxygen species ROS generated as part of the chronic inflammatory state probably further exacerbate anemia in cancer patients.28 ROS include a host of injurious compounds such as superoxide the hydroxyl radical and nitric oxide. Although nitric oxide is a very important biological second messenger out of context the molecule is a potent oxidizing agent. These agents can injure cells by promoting production of lipid and protein peroxides as well as DNA cross-links.29 Heavy oxidant damage leads to cell necrosis. Less severe injury triggers apoptosis with eventual cell death. Hematopoietic precursor cells are very sensitive to oxidant assault. Erythroid precursors appear to be particularly susceptible to this form of injury perhaps because of their abundant iron content. Iron is a natural catalyst in the formation of ROS. Cells have a number of defenses against oxidant injury including enzymes such as superoxide dismutase glutathione .