Blood, 1 April 2003, Vol. 101, No. 7, pp. 2450-2450
Forging iron links
Hepcidin is a tiny protein that packs a lot of punch.
It acts as a potent negative regulator of iron absorption and
mobilization. Mouse hepcidin mRNA levels have been shown to be
exquisitely sensitive to body-iron stores, erythroid demand, hypoxia,
and inflammation. But until recently, little was known about hepcidin
responses in human patients.
Last year we showed that patients with a unique presentation of
the anemia of chronic disease expressed inappropriately high levels of
hepcidin mRNA, and we proposed that hepcidin was responsible for the
abnormalities of iron metabolism (defective absorption, macrophage iron
retention) observed clinically (Weinstein et al, Blood.
2002;100:3776-3781). We speculated that it might play a fundamental
role in the anemia of chronic disease in general. In this issue
Nemeth and colleagues (page 2461) present impressive results that lend
strong support to that conclusion. They find dramatic elevations in
hepcidin protein levels in urine from patients with anemia
and inflammation. There is every reason to believe that serum
hepcidin concentrations are similarly elevated.
Classical teaching implicates inflammatory cytokines in the
pathogenesis of the anemia of chronic disease, and elaborate models have been put forth to explain how they might directly affect iron
distribution and erythropoiesis. But Nemeth et al's discovery that
IL-6 induces hepcidin expression supports a much simpler explanation
for the abnormal iron homeostasis observed in this disorder. Although
it remains to be seen how much of the picture of anemia of chronic
disease can be explained by this one little iron hormone, it now
appears quite possible that cytokine induction of hepcidin expression
might be most of the story.
Nemeth et al have also followed urine hepcidin in a patient with acute
bacterial sepsis. Consistent with its labile regulation in mice and its
role in the anemia of chronic disease, levels are markedly elevated at
presentation, and they normalize as the infection comes under
antibiotic control. This raises the intriguing possibility that
hepcidin might serve as a novel marker for acute bacterial infections.
Nancy C. Andrews and Cindy N. Roy
Harvard Medical School, Howard Hughes Medical
Institute
