Abstract: Poster Presentations |


Seth Rivera, MD, PhD*; Victoria Gabayan, BS; Tomas Ganz, MD, PhD
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University of California, Los Angeles, Los Angeles, CA


Chest. 2007;132(4_MeetingAbstracts):662a. doi:10.1378/chest.132.4_MeetingAbstracts.662a
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PURPOSE: Anemia of inflammation (AI, anemia of chronic disease) is an almost universal finding in the ICU. The iron regulatory hormone hepcidin causes anemia of inflammation by blocking the absorption of iron preventing the release from stores. We have previously demonstrated that IL-6 was necessary and sufficient for the acute regulation of hepcidin and the development of hypoferremia. Furthermore, IL-6 antagonists have been shown to reverse the anemia seen in Castlemans syndrome. In vitro, IL-1 and TNF-α have been shown to upregulate hepcidin. 1) Develop a reproducible mouse model of anemia of inflammation (AI). 2) Test whether IL-6 is necessary in for the regulation of hepcidin and the development of AI.

METHODS: We studied the effects of a single intraperitoneal injection of complete Freund's adjuvant (CFA) on hematologic parameters in the C57/Bl6 mouse. To test whether IL-6 is necessary for the regulation of IL-6 during AI, we also tested this model in IL-6 deficient mice on the same background.

RESULTS: CFA caused acute hypoferremia accompanied by hepcidin elevation. The inflammation lasted for 3 weeks without the mice becoming moribund. At 3 weeks, mice developed significant microcytic anemia accompanied by elevated hepcidin. IL-6 knockout developed more severe anemia and had elevated hepcidin.

CONCLUSION: 1) A single intraperitoneal injection of CFA serves as a reproducible model of anemia of inflammation. 2) IL-6 is not necessary for the regulation of hepcidin or the development of AI.

CLINICAL IMPLICATIONS: IL-6 antagonists will not be effective to prevent or treat AI except in IL-6 dependent conditions such as Castlemans syndrome. Studies are underway using the CFA model to determine whether hepcidin is necessary for the development of AI.

DISCLOSURE: Seth Rivera, No Financial Disclosure Information; No Product/Research Disclosure Information

Wednesday, October 24, 2007

12:30 PM - 2:00 PM




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