Interleukin11

IL-11 is an additional cytokine that has gained approval for general medical use. This cytokine, produced largely by IL-1-activated bone marrow stromal cells and fibroblasts, functions as a haematopoietic growth factor. It stimulates (a) thrombopoiesis (the production of platelets formed by the shedding of fragments of cytoplasm from large bone marrow cells called megakaryocytes; Chapter 10) and (b) growth/differentiation of bone marrow cells, derived from stem cells that have become committed to differentiate into macrophages.

IL-11 is a 23 kDa, 178 amino acid polypeptide. Its receptor appears to be a single-chain 150 kDa transmembrane protein. Binding of IL-11 results in tyrosine phosphorylation of several intracellular proteins, which, in turn, somehow promote the observed biological activities of IL-11.

The rationale for assessing IL-11 as a potential therapeutic agent relates mainly to its ability to induce platelet synthesis. Platelet counts can be significantly lowered due to certain disease conditions and in patients undergoing cancer chemotherapy. Trials in patients receiving chemotherapy illustrated that s.c. administration of IL-11, at levels above 25 ^g per kilogram body weight per day, did stimulate platelet production, at least partially offsetting the chemotherapeutic effects. When administered at levels of 50 ^g kg-1 day-1, a significant increase in the bone marrow megakaryocyte population was noted. At levels in excess of 75 ^g kg-1 day-1, side effects, including fatigue and oedema (tissue swelling due to accumulation of fluid), were also noted.

Neumega is the tradename given to the IL-11-based product approved for the prevention of thrombocytopenia. The product is produced in engineered E. coli cells and is presented as a purified product in freeze-dried format. Excipients include phosphate buffer salts and glycine. It is reconstituted (with water for injections) to a concentration of 5 mg ml-1 before s.c. administration.

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Supplements For Diabetics

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