Biology Reference
In-Depth Information
body load of iron may be excessive yet the presentation is one of functional
iron deficiency, is typical of ACD, the anemia of cancer, and perhaps other
anemias with an inflammatory component. When deficient, and depending
upon the reason for the deficiency, supplementation with oral or intravenous
iron may be relatively straightforward. The move from oral administration of
simple salts like ferrous sulfate towards more complex intravenous forms
of iron resulted from a series of clinical studies, although agreement is not
complete [103, 104]. EPO has not been shown to have a direct role in mobi-
lizing iron from storage organs, but can act indirectly by stimulating hemo-
globin synthesis and drawing iron from storage pools. Although iron may
often be a limiting step in erythropoiesis, it may be corrected by supplemen-
tation. The converse may prove an interesting new use for rHuEPO - in man-
aging inappropriate iron distribution often seen in conditions such as chronic
inflammation and associated with oxidative damage, cognitive impairment,
overt toxicity.
The use of EPO in different species
EPO from mammalian species as diverse as human, hamster, rat, mouse, cat,
lion, dog, horse, sheep, dolphin, and pig has been cloned and sequenced and
found to be remarkably conserved with a minimum identity of 79.8% between
any two of these species [105, 106]. This finding has lead to the experimental
use of rHuEPO in cross-species settings, for instance in anemic feline immun-
odeficiency virus (FIV)-infected cats [107], for idiopathic anemia in dolphins
[108], in blood doping of racehorses [109], in transient brain ischemia in ger-
bils [110], for subarachnoid hemorrhage in rabbits [111], and to study ery-
throkinetics in sheep [112]. Even with the high degree of conservation across
species, the administration of rHuEPO can raise antibodies that may cross-
neutralize endogenous EPO (e.g., in horses [113]). Despite the precise species
match between recombinant and endogenous forms of EPO, instances of
cross-neutralizing antibodies have been reported in humans receiving some
forms of rHuEPO, but not others with identical amino acid sequence. (See
Chapter 14 for further information). It may be the case that even though these
antibodies bind to similar epitopes on the protein backbone of rHuEPO and
endogenous EPO, their induction is dependent on other factors such as autoim-
mune disease or manufacturing or formulation methods resulting in protein
aggregation or degradation. (See Chapter 15 by Elliott for further information.)
Conclusions
rHuEPO is, for the most part, an erythroid stimulus that has found widespread
use in patients with EPO-limited anemia. It has proven useful in treating ane-
mias where endogenous EPO concentrations may not be abnormally low.
