Biology Reference
In-Depth Information
Table 3. Factors affecting rHuEPO response rates
Condition
EPO-response limiting factor [Ref]
Renal failure [142]
Iron
Deficiency [143]
Overload [144]
Soluble EPOR [101]
Inflammatory cytokines; inhibition of CFU-E [145]
Endogenous inhibitors [146]
Oxidative damage to red blood cells [147]
Aluminum toxicity [148]
Oncology
Marrow infiltration by tumor, hemolysis, nutritional deficiency [59]
Inflammatory cytokines [96]
Iron [149]
Anemia-inducing factors [150]
Marrow injury [151]
Systemic lupus
Multiple causes: anemia of chronic disease, iron deficiency,
erythematosus
hemolysis [97]
Antibodies to EPO [152]
Concurrent therapies
Inhibition of erythropoiesis by
Cyclosporin [153]
IFN [154]
AZT [155]
Anemia of chronic
Reduced EPO production and effectiveness, iron metabolism [156]
disorders
Pure red cell aplasia
Antibodies (Mayeux and Casadevall, this volume)
Multiple causes [157]
AZT, zidovudine; IFN, interferon; CFU-E, erythroid colony-forming unit; EPO, erythropoietin.
raised in response to administered rHuEPO with serious consequences (see
Chapter 14) and may include life-long refractoriness to rHuEPO and endoge-
nous EPO and a long-term dependence on blood transfusions for survival.
Soluble EPOR is a truncated version of the full-length membrane-bound ver-
sion that has been suggested to act as a competitive inhibitor of the cell-borne
form of the receptor and can limit the response to injected rHuEPO [100, 101].
Several such confounding factors likely to be found in various indications are
listed in Table 3.
Interaction with iron
Iron is a vital component of hemoglobin and limitations on its supply can com-
promise the ability of erythropoietic cells to synthesize hemoglobin.
Paradoxically, iron is a poisonous metal for which most mammals, including
humans, have highly evolved strategies to ameliorate its toxicities. Iron defi-
ciency is commonly discussed,although the body's treatment of iron as a toxin
can lead to its deposition as relatively inert forms (such as ferritin or hemo-
siderin) in various tissues [102]. This iron maldistribution situation, where the
