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Biotechnology and Bioengineering, Vol.44, No.9, 1023-1030, 1994
Removing of Cytokines from Hsa-Containing Solutions by Adsorption Onto Silica
Septic shock syndrome is a potentially fatal medical condition that is associated with elevated blood levels of low molecular weight proteins known as cytokines. Adsorption was investigated as a potential method for removing cytokines from blood. Saline with 50 mg/mL human serum albumin (HSA) spiked with pathological concentrations (ng-pg/mL) of radiolabeled cytokine was used to study cytokine adsorption. Adsorption isotherms were linear in the pathological concentration range, with adsorption constants ranging from 33.0 mL/g to 173 mL/g for tumor necrosis factor (TNF-alpha), interleukin-8 (IL-8), interleukin-6 (IL-6), and C3a. Adsorption constants were also determined for interleukin-1 alpha (IL-1 alpha), IL-1 beta, and interferon-gamma (IFN-gamma). The adsorption of cytokines by several different silica adsorbents were investigated. Increased concentrations of NaCl reduced cytokine adsorption, but did not completely eliminate adsorption even at high concentrations, suggesting that adsorption was not entirely electrostatic in nature. Possible mechanisms of cytokine adsorption are discussed. Data for batch adsorption for TNF-alpha was used to estimate the minimum amount of silica required to treat septic shock. It was concluded that a silica adsorbent has a sufficiently high capacity to be used for hemoperfusion. Adsorption of myoglobin and cytochrome c was also investigated as possible marker proteins for future dynamic adsorption studies in hemoperfusion devices.
Keywords:TUMOR-NECROSIS-FACTOR;SEPTIC SHOCK;AFFINITY SEPARATIONS;INTERLEUKIN-1;SERUM;PURIFICATION;PROTEIN;DISEASE;SEPSIS;PLASMA