Effect of a novel adsorbent on cytokine responsiveness to uremic plasma.
BACKGROUND
Middle molecules such as beta2-microglobulin (beta2M) and advanced glycation end products (AGE)-modified proteins contribute to inflammation in uremia. The BetaSorb column is a new adsorptive device, which contains copolymeric beads, suitable for removal of beta2M and other middle molecules. We assessed the effect of this column on the bioreactivity of uremic plasma, as measured by cytokine responsiveness.


METHODS
Uremic plasma was perfused in vitro through the column (10 mL/min) and samples were collected after 10 to 30 passes. Endotoxin-stimulated tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) production by THP-1-derived monocytes was measured following brief exposure to uremic plasma. beta2M levels were measured. The contribution of AGE-modified proteins to the bioreactivity of uremic plasma was explored.


RESULTS
TNF-alpha and IL-10 production markedly decreased after 30 passes (629 +/- 78 vs. 144 +/- 62 pg/mL; 207 +/- 25 vs. 117 +/- 23 pg/mL; P=0.04). The column removed beta2M efficiently with a marked decline in plasma levels by 99% after 30 passes. Neutralization of AGE receptor (RAGE) resulted in a further reduction in the bioreactivity of uremic plasma. This was observed with nonperfused, as well as perfused, uremic plasma, suggesting that AGE-modified proteins were biologically active and still present after perfusion.


CONCLUSIONS
The sorbent beads removed uremic solute(s) that prime monocytes to enhanced cytokine production. Removal of beta2M was efficient, and of native and AGE-modified middle molecules likely.
Morena
Marion D
MD
Department of Medicine, Tupper Research Institute, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
Guo
Daqing
D
Balakrishnan
Vaidyanathapuram S
VS
Brady
James A
JA
Winchester
James F
JF
Jaber
Bertrand L
BL
D000906:Antibodies / Q000494:pharmacology; D015415:Biomarkers; D045744:Cell Line, Tumor; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D008863:Microspheres; D009000:Monocytes / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000276:immunology; D016060:Sorption Detoxification / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014511:Uremia / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D001613:beta 2-Microglobulin / Q000097:blood
D000906:Antibodies; D015415:Biomarkers; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D016753:Interleukin-10