Anemia interleukin

Cytokines such as interferons are used for the treatment of hepatitis, cancer, and lymphoma interleukins are used to enhance immune response and growth factors are used for the treatment of anemia and regulation of tumor angiogenesis. 

The most common side effects of interleukin-11 are fatigue, headache, dizziness, and cardiovascular effects. The cardiovascular effects include anemia (due to hemodilution), dyspnea (due to fluid accumulation in the lungs), and transient atrial arrhythmias. Hypokalemia has also been seen in some patients. All of these adverse effects appear to be reversible. In the limited clinical trial data available thus far, recombinant thrombopoietin appears to be well tolerated. 

Autoimmune diseases have been reported to be more frequent in human subjects treated with several recombinant cytokines [38], For instance, increased titers or the new occurrence of autoantibodies have been observed in hepatitis C patients treated with the recombinant interferons-alpha (IFNa). Quite a few clinical case reports describe the development of organ-specific as well as systemic autoimmune diseases including systemic lupus erythematosus, insulin-dependent type I diabetes mellitus, autoimmune thrombocytopenia, autoimmune hemolytic anemia, myasthenia gravis, and autoimmune thyroiditis in patients under IFNa therapy. Although the mechanism involved is not fully elucidated, the available data support the pathogenic potential of IFNa in autoimmunity [31]. In contrast, autoimmune effects associated with IFNp therapy are thought to be of lesser concern based on the current clinical evidence [38], Thyroid autoimmunity in contrast to other autoimmune diseases is frequent in patients treated with recombinant interleukin-2 (rIL-2). Thus, among 281 previously euthyroid cancer patients treated with rIL-2, up to 41%... 

Musto P, Sanpaolo G, D Arena G, Scalzulli PR, Matera R, Falcone A, Bodenizza C, Perla G, Carotenuto M. Adding growth factors or interleukin-3 to erythropoietin has limited effects on anemia of transfusion-dependent patients with myelodysplastic syndromes unresponsive to erythropoietin alone. Haematologica 2001 86(1) 44-51. 

Interferon gamma was supposedly the cause of asymptomatic non-immune hemoljdic anemia in one patient receiving both interleukin-2 and interferon gamma (14). 

Thrombophlebitis was recorded in 45% of patients treated for advanced ovarian cancer who also received intravenous interleukin-3 (14), and deep venous thromboses were reported in children treated with maintenance interleukin-3 for Diamond-Blackfan anemia (15). In addition, one smoking breast-cancer patient developed severe hypotension and cerebellar and superior mesenteric thrombosis after subcutaneous interleukin-3 administration (SEDA-19, 340). Collectively, these case reports suggest that interleukin-3 may contribute to the development of thrombosis, but a possible increased risk of thrombosis with interleukin-3 remains to be demonstrated. 

There has been one case of bone marrow histiocytosis in a patient treated with interleukin-3 for refractory aplastic anemia (SED-13,1109). 

A 66-year-old man with radiation-induced aplastic anemia and myelodysplastic features failed to respond to multiple therapeutic regimens. A trial of recombinant human interleukin-3 was begun, but he had transient shortness of breath and hypotension after the first subcutaneous injection. On the next day, 2 hours after the second dose, he had restlessness, dyspnea, spasticity, wheezing, cyanosis, hyperthermia, tachycardia, and hypotension (70/50 mmHg). Full recovery was obtained with fluids, adrenaline, promethazine, and glucocorticoids. 

Gillio AP, Faulkner LB, Alter BP, Reilly L, Klafter R, Heller G, Young DC, Lipton JM, Moore MA, O Reilly RJ. Treatment of Diamond-Blackfan anemia with recombinant human interleukin-3. Blood 1993 82(3) 744-51. 

Dose-dependent and reversible normochromic normo-cjrtic anemia was consistently noted within several days after starting interleukin-6, and required blood transfusion at the highest dose (3). Hemodilution was considered as the primary mechanism. 

Nieken J, Mulder NH, Buter J, Vellenga E, Limburg PC, Piers DA, de Vries EG. Recombinant human interleukin-6 induces a rapid and reversible anemia in cancer patients. Blood 1995 86(3) 900-5. 

Single cases of agranulocytosis and Coombs negative hemolytic anemia have been attributed to twice-weekly mterleukin-12 in 28 patients with renal cell cancer or melanoma (2). The patients responded only to cyclophosphamide and/or glucocorticoids, and the causative role of interleukin-12 was therefore inconclusive. 

ACD is a hypoprolrferative anemia that has traditionally been associated with infectious or inflammatory processes, tissue injury, or conditions associated with the release of proinflammatory cytokines. Alternative names include anemia of inflammation and cytokine-mediated anemia. The pathogenesis of the anemia of chronic disorders is based on three abnormalities shortened erythrocyte survival, impaired marrow response, and disturbance of iron metabolism. Pathologically, the RBCs have a shortened life span, and the bone marrow s capacity to respond to EPO is inadequate to maintain normal Hgb concentration. The cause of this defect is still uncertain, but appears to involve a block in the release of iron from the reticuloendothelial cells of the marrow. Various cytokines, such as interleukin-1, interferon-y, and tumor necrosis factor released during these illnesses may inhibit the production or action of EPO or the production of RBCs. ... 

Hematopoietic growth factors also have been produced in mammalian cell cultures by recombinant DNA techniques. Erythropoietin can be used in certain types of anemias to stimulate the production of red blood cells. Colony-stimulating factors (CSFs) and interleukins (ILs) can be used after bone marrow transplants and after chemotherapy to stimulate white blood cell production and decrease the risk of infection. 

Figure 33-1. Drugs used in the treatment of anemias and blood cell deficiencies. G-CSF, granulocyte colony-stimulating factor GM-CSF, granulocyte-macrophage colony-stimulating factor IL-11, interleukin-11.

For our model system, hepatic ferritin gene expression was monitored in response to interleukin-1 (IL-1) [71]. IL-1 was found to significantly increase ferritin translation by signaling though a novel translation enhancer element, the acute box motif, downstream from the IREs at the 5 cap site [45, 72]. This acute box motif is located immediately downstream from Iron-responsive Element in the 5 untranslated regions of both the L- and H-ferritin transcripts [73], and was also found to be present in front of the start codon in the APP transcript [47]. This observation was consistent with the pattern of both APP and ferritin expression in response to inflammation during both Alzheimer s disease and the anemia associated with chronic disease. 

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