The novel iron chelator, DIBI, attenuates inflammation and improves outcome in colon ascendens stent peritonitis-induced experimental sepsis

Issue title: Selected papers of the 39th Conference of the German Society for Clinical Microcirculation and Hemorheology, 6-7 November 2020, Hannover, Germany

Guest editors: B. Hiebl, A. Krüger-Genge and F. Jung

Article type: Research Article

Authors: Fokam, Danielle^a | Aali, Maral^a | Dickson, Kayle^b | Scott, Cassidy^c | Holbein, Bruce^{b; d} | Zhou, Juan^e | Lehmann, Christian^{a; b; c; e; *}

Affiliations: [a] Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada | [b] Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada | [c] Department of Pharmacology, Dalhousie University, Halifax, NS, Canada | [d] Chelation Partners Inc., Halifax, NS, Canada | [e] Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada

Correspondence: [*] Corresponding author: Christian Lehmann, E-mail: [email protected].

Abstract: BACKGROUND:Sepsis is the result of a dysregulated host immune response to an infection. An ideal therapy would target both the underlying infection and the dysregulated immune response. DIBI, a novel iron-binding polymer, was specifically developed as an antimicrobial agent and has also demonstrated in vivo anti-inflammatory properties. OBJECTIVE:This study aimed to further investigate the effects of DIBI with and without the antibiotic imipenem (IMI) in colon ascendens stent peritonitis (CASP)-induced experimental sepsis. METHODS:Vehicle, DIBI and/or IMI were administered in C57BL/6 mice after CASP surgery. Intestinal leukocyte activation and capillary perfusion was evaluated by intravital microscopy. Moreover, bacterial load in peritoneal lavage fluid and blood, and plasma cytokine levels were assessed. In a second series of experiments, surgery to repair the colon was performed at 5 hr and these mice were followed for long-term survival over 7 days. RESULTS:DIBI reduced leukocyte adhesion, improved capillary blood flow, and decreased key plasma cytokines levels. DIBI also improved survival of infected mice and greatly improved IMI efficacy. Survivors treated with IMI and DIBI were found to be free of systemic infection. CONCLUSIONS:DIBI has promising potential for sepsis treatment including its use as a sole or an adjunct therapeutic with antibiotics.

DOI: 10.3233/CH-209207

Journal: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 241-261, 2020