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 Inflammation.
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 peptidoglycan-polysaccharide polymers.
- TNF-alpha blockade is known to partially reverse the effects of ACD in some patients.
- 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 weekly.
- Paw swelling volume was checked once weekly as a surrogate for systemic inflammation.
- 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 these parameters.
- The combination enhances total serum iron and tranferrin bound serum iron
- 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.