Novel Erythropoeisis Stimulating Protein (Aranesp) Enhances Pegylated
Soluble Tumor Necrosis Factor Receptor Type 1 (PEG sTNF-R1) Alleviation of
Anemia of Chronic Disease (ACD) in a Rodent Model of Systemic
Reviewer: Walter F. Sall, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 8, 2001
Presenter: Greg Stoney
Affiliation: Amgen Inc.
Anemia of Chronic Disease is commonly associated with several chronic
inflammatory disease states. ACD has a multifactorial pathogenesis
mediated by multiple inflammatory cytokines.
Aranesp is a novel erythropoetin analogue with a sustained duration of
action, known to alleviate anemia.
ACD can be replicated in Lewis rats immunized with
TNF-alpha blockade is known to partially reverse the effects of ACD in
This study is designed to test the effects of Aranesp and the
TNF-alpha blocking agent PEGsTNF-RI on this rat model of ACD
Materials and Methods
Lewis rats were immunized with PG-APS or carrier immunizations
Rats were treated for two weeks with Aranesp alone, PEG sTNF-RI alone
or a combination of the two agents.
a CBC was checked twice weekly. Serum iron levels were checked once
Paw swelling volume was checked once weekly as a surrogate for
Combined therapy reduced inflammation induced paw swelling. Either
monotherapy did not have a significant effect.
Combined therapy alleviates ACD, with a mean increase in hgb of 4.1.
Aranesp alone had no significant effect.
Combined therapy improves multiple RBC parameters including: MCV,
reticulocyte count and MCH. No effect with either monotherapy was seen on
The combination enhances total serum iron and tranferrin bound
Aranesp alone does not alleviate ACD.
PEG sTNF-RI alone reduces inflammation but not ACD.
Combination therapy normalized hemoglobin levels, reticulocyte counts,
MCH, MCV and TSI compared to controls and either monotherapy.
mechanism of synergy is enhanced erythropoietic response and
increased usable transferrin bound serum iron.