The aim of the present study was to develop and investigate nanoporous activated carbon materials for their ability to adsorb inflammatory cytokines directly from blood, for a range of therapeutic applications, including: systemic inflammatory response syndrome (SIRS) related to sepsis, cardio-pulmonary by-pass surgery, or ischemic reperfusion injury. Building on the previously established relationship between the porous structure of beaded polymer-derived activated carbon and its capacity to adsorb inflammatory molecules, we have developed and characterized monolithic porous carbon columns produced from the same polymer precursor matrix as carbon microbeads. The monolithic columns developed were assessed for their ability to adsorb inflammatory molecules from blood in a circulating system. Preliminary findings demonstrated good removal of the inflammatory cytokines IL-8 (100% removal), IL-6 (80% removal), and TNF (51% removal) from blood. The efficiency of cleansing is dependent on the size of the adsorbed molecule and the porous structure of the monolith, highlighting their potential for use as a hemoadsorption device.
AngusD.C., Linde-ZwirbleW.T., LidickerJ., ClermontG., CarcilloJ., PinskyM.R.Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.Crit Care Med.2001; 29(7): 1303–1310.
2.
LevyM.M., ArtigasA., PhillipsG.S.Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study.Lancet Infect Dis.2012; 12(12): 919–924.
3.
LevyM.M., DellingerR.P., TownsendS.R.The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis.Crit Care Med.2010; 38(2): 367–374.
4.
GaieskiD.F., MikkelsenM.E., BandR.A.Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department.Crit Care Med.2010; 38(4): 1045–1053.
5.
MartinG.S.Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes.Expert Rev Anti Infect Ther.2012; 10(6): 701–706.
6.
LeviM.Activated protein C in sepsis: a critical review.Curr Opin Hematol.2008; 15(5): 481–486.
7.
ColeL., BellomoR., DavenportP.The effect of coupled haemofiltration and adsorption on inflammatory cytokines in an ex vivo model.Nephrol Dial Transplant.2002; 17(11): 1950–1956.
8.
KobeY., OdaS., MatsudaK., NakamuraM., HirasawaH.Direct hemoperfusion with a cytokine-adsorbing device for the treatment of persistent or severe hypercytokinemia: a pilot study.Blood Purif.2007; 25(5-6): 446–453.
9.
KawatsuM., WadaJ., KitanoM.Effects of a new extra-corporeal system using CTR on mortality and inflammatory responses to bacterial toxin-induced multiple organ dysfunction syndrome in rabbits.Blood Purif.2006; 24(3): 327–334.
10.
NakamuraM., OdaS., SadahiroT.Treatment of severe sepsis and septic shock by CHDF using a PMMA membrane hemofilter as a cytokine modulator.Contrib Nephrol.2010; 166: 73–82.
11.
HowellC.A., SandemanS.R., PhillipsG.J.The in vitro adsorption of cytokines by polymer-pyrolysed carbon.Biomaterials.2006; 27(30): 5286–5291.
12.
SandemanS.R., HowellC.A., PhillipsG.J.Assessing the in vitro biocompatibility of a novel carbon device for the treatment of sepsis.Biomaterials.2005; 26(34): 7124–7131.
13.
BarnesL.M., PhillipsG.J., DaviesJ.G.The cytotoxicity of highly porous medical carbon adsorbents.Carbon.2009; 47(8): 1887–1895.
14.
SandemanS.R., HowellC.A., MikhalovskyS.V.Inflammatory cytokine removal by an activated carbon device in a flowing system.Biomaterials.2008; 29(11): 1638–1644.
15.
YushinG., HoffmanE.N., BarsoumM.W.Cytokine Meso-porous carbide-derived carbon with porosity tuned for efficient adsorption of cytokine.Biomaterials.2006; 27(34): 5755–5762.
OdaS., HirasawaH., ShigaH.Cytokine adsorptive property of various adsorbents in immunoadsorption columns and a newly developed adsorbent: an in vitro study.Blood Purif.2004; 22(6): 530–536.
18.
ReedC., FuZ.Q., WuJ.Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2.Protein Eng.1997; 10(10): 1101–1107.
19.
SomersW., StahlM., SeehraJ.S.1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor di-merization and signaling.EMBO J.1997; 16(5): 989–997.
20.
BaldwinE.T., WeberI.T., St CharlesR.Crystal structure of interleukin 8: symbiosis of NMR and crystallography.Proc Natl Acad Sci U S A.1991; 88(2): 502–506.
21.
TaniguchiT., HiraiF., TakemotoY.A novel adsorbent of circulating bacterial toxins and cytokines: the effect of direct hemoperfusion with CTR column for the treatment of experimental endotoxemia.Crit Care Med.2006; 34(3): 800–806.
22.
NagakiM., HughesR.D., KeaneH.M., LauJ.Y.N., WilliamsR.In vitro plasma perfusion through adsorbents and plasma ultrafiltration to remove endotoxin and cytokines.Circ Shock.1992; 38(3): 182–188.
23.
SongM., WinchesterJ., AlbrightR.L., CapponiV.J., ChoquetteM.D., KellumJ.A.Cytokine removal with a novel adsorbent polymer.Blood Purif.2004; 22(5): 428–434.
24.
PengZ.Y., CarterM.J., KellumJ.A.Effects of hemoadsorption on cytokine removal and short-term survival in septic rats.Crit Care Med.2008; 36(5): 1573–1577.
25.
DiLeoM.V., FisherJ.D., BurtonB.M., FederspielW.J.Selective improvement of tumor necrosis factor capture in a cytokine hemoadsorption device using immobilized anti-tumor necrosis factor.J Biomed Mater Res B Appl Biomater.2011; 96(1): 127–133.
MiwaK., FukuyamaM., IdaN., IgarashiH., UchiyamaT.Preparation of a superantigen-adsorbing device and its superantigen removal efficacies in vitro and in vivo.Int J Infect Dis.2003; 7(1): 21–26.
28.
FenwickP., RyanC., SriskandanS., CohenJ.Application of a rat model of streptococcal shock to evaluate on-line he-moperfusion and removal of circulating superantigens.Crit Care Med.2003; 31(1): 171–178.
29.
MiwaK., FukuyamaM., MatsunoN., ShimadaK., IkedaK., Ike-daT.Physiological response to superantigen-adsorbing he-moperfusion in toxin-concentration-controlled septic swine.Blood Purif.2006; 24(3): 319–326.
