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 protein s known as cytokines. Adsorption was investigated as a potential metho d for removing cytokines from blood. Saline with 50 mg/mL human serum albumin (HSA) spiked with pathological concentrations (ng-pg/mL) of ra diolabeled cytokine was used to study cytokine adsorption. Adsorption isotherms were linear in the pathological concentration range, with ad sorption constants ranging from 33.0 mL/g to 173 mL/g for tumor necros is factor (TNF-alpha), interleukin-8 (IL-8), interleukin-6 (IL-6), and C3a. Adsorption constants were also determined for interleukin-1 alph a (IL-1 alpha), IL-1 beta, and interferon-gamma (IFN-gamma). The adsor ption of cytokines by several different silica adsorbents were investi gated. Increased concentrations of NaCl reduced cytokine adsorption, b ut 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 ba tch adsorption for TNF-alpha was used to estimate the minimum amount o f silica required to treat septic shock. It was concluded that a silic a adsorbent has a sufficiently high capacity to be used for hemoperfus ion. Adsorption of myoglobin and cytochrome c was also investigated as possible marker proteins for future dynamic adsorption studies in hem operfusion devices. (C) 1994 John Wiley & Sons, Inc.