Parenteral iron therapy exacerbates experimental sepsis Rapid Communication
- 1 June 2004
- journal article
- Published by Elsevier BV in Kidney International
- Vol. 65 (6), 2108-2112
- https://doi.org/10.1111/j.1523-1755.2004.00742.x
Abstract
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; 2mg). Nonseptic mice ± iron therapy served as controls. Plasma tumor necrosis factor-α (TNF-α) levels were assessed 2hours postinjections (serving as an inflammatory marker). Oxidative stress was gauged in heart or kidney tissue (at either 4 or 24hours) by heme oxygenase-1 (HO-1) mRNA or protein levels. Overall sepsis severity was assessed by morbidity/mortality rates (at 24hours). 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-α levels (from 0 to 2.3pg/mL; P = 0.01). However, iron approximately doubled the TNF-α increments which arose from the septic state (1400 → 2600pg/mL). Neither sepsis alone, nor iron alone, induced any mortality and no mice became moribund (0/24 mice). However, when iron + sepsis were combined, ∼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-α release. However, when iron is given during experimental sepsis, profound increases in both processes, and ∼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.Keywords
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