The Effect of Manuka Honey on dHL-60 Cytokine, Chemokine, and Matrix-Degrading Enzyme Release under Inflammatory Conditions.

Benjamin A Minden‐Birkenmaier ,Matthew Smeltzer ,Marko Radic ,Meghan Meadows ,Richard A Smith ,Kasyap Cherukuri,Gary L Bowlin

doi:10.20900/mo.20190005

Benjamin A Minden‐Birkenmaier , Matthew Smeltzer + Show 5 more

Open Access

https://doi.org/10.20900/mo.20190005

Copy DOI

Abstract

A large body of in vivo and in vitro evidence indicates that Manuka honey resolves inflammation and promotes healing when applied topically to a wound. In this study, the effect of two different concentrations (0.5% and 3% v/v) of Manuka honey on the release of cytokines, chemokines, and matrix-degrading enzymes from neutrophils was examined using a differentiated HL-60 cell line model in the presence of inflammatory stimuli. The results indicate that 0.5% honey decreased TNF-α, IL-1β, MIP-1α, MIP-1β, IL-12 p70, MMP-9, MMP-1, FGF-13, IL-1ra, and IL-4 release, but increased MIP-3α, Proteinase 3, VEGF, and IL-8 levels. In contrast, 3% honey reduced the release of all analytes except TNF-α, whose release was increased. Together, these results demonstrate a dose-dependent ability of Manuka honey to modify the release of cytokines, chemokines, and matrix-degrading enzymes that promote or inhibit inflammation and/or healing within a wound. The findings of this study provide further guidance for the future use of Manuka honey in wounds or tissue engineering templates. Future in vivo investigation is warranted to validate the in vitro results and translate these results to physiologically relevant environments.

Highlights

Neutrophils, the first-responding leukocytes which enter a wound site soon after injury, orchestrate the initiation, amplification, and resolution of the inflammatory response
The matrix metalloproteinase (MMP)-1 and vascular endothelial growth factor (VEGF) data indicate an increase in release in the granulocytemacrophage colony-stimulating factor (GM-CSF)-stimulated group relative to non-stimulated control, this group is much lower than the LPS-stimulated group in the MMP-1 results
While our results indicate that 3% honey increases tumor necrosis factor (TNF)-α release at both 3 and 24 hours, it is possible that the overall drop in neutrophil number, coupled with the decrease in release of all other factors measured in this study except IL-8, causes the inflammation decrease observed in vivo

Summary

Introduction

Neutrophils, the first-responding leukocytes which enter a wound site soon after injury, orchestrate the initiation, amplification, and resolution of the inflammatory response. In addition to their role as phagocytes, in which they engulf and destroy invading bacteria, neutrophils release a host of molecular agents which affect the inflammatory state of the wound. Persistent, non-resolving inflammatory neutrophil activity has been implicated in chronic inflammation that impedes wound healing and causes sepsis [11,12,13]. This activity has been linked to inflammatory diseases such as rheumatoid arthritis and atherosclerosis [14,15,16]. It is necessary to develop and optimize treatments to shift neutrophils from this inflammatory state to an anti-inflammatory state to resolve such pathological inflammation

Methods

Results

Discussion

Conclusion