Honokiol increases CD4+ T cell activation and decreases TNF but fails to improve survival following sepsis

• Type of Material: Article
• Authors: Nathan J. Klingensmith, Emory University; Ching-Wen Chen, Emory University; Zhe Liang, Emory University; Eileen Burd, Emory University; Alton B Farris III, Emory University; Jack Arbiser, Emory University; Mandy L Ford, Emory University; Craig Coopersmith, Emory University
• Language: English
• Date: 2018-08-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Copyright 2017 by the Shock Society.
• Final Published Version (URL): http://dx.doi.org/10.1097/SHK.0000000000001021
• Title of Journal or Parent Work: Shock
• ISSN: 1073-2322
• Volume: 50
• Issue: 2
• Start Page: 178
• End Page: 186
• Grant/Funding Information: This work was supported by funding from the National Institutes of Health (GM095442, GM072808, GM104323, GM113228, GM109779, AR47901)
• Keywords: intestine; SEPTIC SHOCK; lymphocyte; Critical Care Medicine; RISK; THERAPY; survival; Science & Technology; Hematology; Life Sciences & Biomedicine; Cardiovascular System & Cardiology; PATHWAY; MIGRATION; Peripheral Vascular Disease; ENDOTOXEMIA; Honokiol; TNF; MORTALITY; Activation; sepsis; INJURY; Surgery; General & Internal Medicine; PUNCTURE; inflammation
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree that has been used in traditional Chinese and Japanese medicine, and has more recently been investigated for its anti-inflammatory and antibacterial properties. Honokiol has previously been demonstrated to improve survival in sepsis models that have rapid 100% lethality. The purpose of this study was to determine the impact of Honokiol on the host response in a model of sepsis that more closely approximates human disease. Male and female C57BL/6 mice underwent cecal ligation and puncture to induce polymicrobial intra-abdominal sepsis. Mice were then randomized to receive an injection of either Honokiol (120mg/kg/day) or vehicle and were sacrificed after 24h for functional studies or followed 7 days for survival. Honokiol treatment after sepsis increased the frequency of CD4 + T cells and increased activation of CD4 + T cells as measured by the activation marker CD69. Honokiol also increased splenic dendritic cells. Honokiol simultaneously decreased frequency and number of CD8 + T cells. Honokiol decreased systemic tumor necrosis factor without impacting other systemic cytokines. Honokiol did not have a detectable effect on kidney function, lung physiology, liver function, or intestinal integrity. In contrast to prior studies of Honokiol in a lethal model of sepsis, Honokiol did not alter survival at 7 days (70% mortality for Honokiol vs. 60% mortality for vehicle). Honokiol is thus effective in modulating the host immune response and inflammation following a clinically relevant model of sepsis but is not sufficient to alter survival.