title: IL-6 adsorption dynamics in hemoadsorption beads studied using confocal laser scanning microscopy.
abstract: Sepsis is characterized by a systemic inflammatory response caused by infection, and can result in organ failure and death. Removal of inflammatory mediators such as cytokines from the circulating blood is a promising treatment for severe sepsis. We are developing an extracorporeal hemoadsorption device to remove cytokines from the blood using biocompatible, polymer sorbent beads. In this study, we used confocal laser scanning microscopy (CLSM) to directly examine adsorption dynamics of a cytokine (IL-6) within hemoadsorption beads. Fluorescently labeled IL-6 was incubated with sorbent particles, and CLSM was used to quantify spatial adsorption profiles of IL-6 within the sorbent matrix. IL-6 adsorption was limited to the outer 15 microm of the sorbent particle over a relevant clinical time period, and intraparticle adsorption dynamics was modeled using classical adsorption/diffusion mechanisms. A single model parameter, alpha = q(max) K/D, was estimated by fitting CLSM intensity profiles to our mathematical model, where q(max) and K are Langmuir adsorption isotherm parameters, and D is the effective diffusion coefficient of IL-6 within the sorbent matrix. Given the large diameter of our sorbent beads (450 microm), less than 20% of available sorbent surface area participates in cytokine adsorption. Development of smaller beads may accelerate cytokine adsorption by maximizing available surface area per bead mass.
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Kimmel
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Gibson
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.forename: William J
authors.initials: WJ
authors.lastname: Federspiel
mesh_terms: D000327:Adsorption; D000818:Animals; D003627:Data Interpretation, Statistical; D005456:Fluorescent Dyes; D005544:Forecasting; D015850:Interleukin-6 / Q000737:chemistry / Q000302:isolation & purification*; D007700:Kinetics; D018613:Microscopy, Confocal; D008863:Microspheres; D015233:Models, Statistical; D011137:Polystyrenes; D016062:Porosity; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D015850:Interleukin-6; D011137:Polystyrenes; D011994:Recombinant Proteins; C432006:divinylbenzene-polystyrene copolymer