Inflammation and sickle cell anemia

Inflammatory processes play a key role in the initiation of the acute painful vaso-occlusive crises that constitute the main cause of hospitalization in individuals with sickle cell anemia, as well as many of its numerous complications, including autosplenectomy, pulmonary hypertension, acute chest syndrome, leg ulcers, nephropathy and stroke. Ischemia-reperfusion injury (due to microvascular and macrovascular occlusions), membrane alterations of the sickle red blood cell, and hemolysis may all trigger endogenous proinflammatory signals (damage-associated molecular patterns-DAMPs) that lead to the vicious circle of pan-cellular activation, inflammatory mediator release, leukocyte recruitment and occlusive mechanisms that result in the chronic inflammatory state that is associated with sickle cell anemia. We, herein, review the probable primary inflammatory triggers that initiate inflammatory mechanisms in the disease and postulate the cells and molecules that may contribute to establish chronic inflammation. The anti-inflammatory effects of hydroxyurea are discussed, as are novel anti-inflammatory approaches currently under study.