Sepsis / 60% mortality / iron




IRONJUSTICE@AOL.COMDOE (DOE) 2004-05-20 14:48:00

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when iron is given during experimental sepsis approximately 60% mortality,
result.
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Kidney Int. 2004 Jun;65(6):2108-12. Related Articles, Links


Parenteral iron therapy exacerbates experimental sepsis Rapid Communication.

Zager RA, Johnson AC, Hanson SY.

Department of Medicine, the University of Washington, and the Fred Hutchinson
Cancer Research Center, Seattle, Washington.

Parenteral iron therapy exacerbates experimental sepsis. Background. Catalytic
iron can potentiate systemic inflammation via its pro-oxidant effects. This
raises the possibility that parenteral iron administration might exacerbate a
concomitant septic state. This study sought to experimentally test this
hypothesis. Methods. Male CD-1 mice were subjected to experimental sepsis via
intraperitoneal injection of heat-killed Escherichia coli+/- concomitant
intravenous iron sucrose (Venofer; 2 mg). Nonseptic mice +/- iron therapy
served as controls. Plasma tumor necrosis factor-alpha (TNF-alpha) levels were
assessed 2 hours postinjections (serving as an inflammatory marker). Oxidative
stress was gauged in heart or kidney tissue (at either 4 or 24 hours) by heme
oxygenase-1 (HO-1) mRNA or protein levels. Overall sepsis severity was assessed
by morbidity/mortality rates (at 24 hours). Results. Iron alone or sepsis alone
each induced oxidant stress in heart and kidney (HO-1 mRNA/protein increases).
When iron and E. coli were coadministered, additive or synergistic HO-1
mRNA/protein increments resulted. Iron injection alone only slightly raised
TNF-alpha levels (from 0 to 2.3 pg/mL; P= 0.01). However, iron approximately
doubled the TNF-alpha increments which arose from the septic state (1400 -->
2600 pg/mL). Neither sepsis alone, nor iron alone, induced any mortality and no
mice became moribund (0/24 mice). However, when iron + sepsis were combined,
approximately 60% of mice either died (5/12) or developed a moribund (2/12)
state (P= 0.005). Conclusion. Parenteral iron administration can induce
systemic oxidative stress and modest TNF-alpha release. However, when iron is
given during experimental sepsis, profound increases in both processes, and
approximately 60% mortality, result. Given that renal failure patients have
decreased antioxidant defenses and intermittently develop bacteremia, the
potential for parenteral iron therapy to exacerbate clinical sepsis needs to be
addressed.

PMID: 15149323 [PubMed - in process]

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