Parenteral iron therapy exacerbates experimental sepsis.

Abstract

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.

• Authors: Richard A Zager, Ali C M Johnson, Sherry Y Hanson
• Journal: Kidney international (Kidney Int) Vol. 65 Issue 6 Pg. 2108-12 (Jun 2004) ISSN: 0085-2538 [Print] United States
• PMID: 15149323 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Endotoxins
• Membrane Proteins
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• endotoxin, Escherichia coli
• Iron
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1
• Hmox1 protein, mouse

Topics

• Animals
• Endotoxins (toxicity)
• Heme Oxygenase (Decyclizing) (genetics, metabolism)
• Heme Oxygenase-1
• Inflammation (etiology, genetics, metabolism)
• Injections, Intravenous
• Iron (administration & dosage, toxicity)
• Kidney (metabolism)
• Male
• Membrane Proteins
• Mice
• Myocardium (metabolism)
• Oxidative Stress (drug effects)
• RNA, Messenger (genetics, metabolism)
• Sepsis (etiology, genetics, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)