Manuka honey modulates the release profile of a dHL-60 neutrophil model under anti-inflammatory stimulation.

Manuka honey, a wound treatment used to eradicate bacteria, resolve inflammation, and promote wound healing, is a current focus in the tissue engineering community as a tissue template additive. However, Manuka honey's effect on neutrophils during the inflammation-resolving phase has yet to be examined. This study investigates the effect of 0.5% and 3% Manuka honey on the release of cytokines, chemokines, and matrix-degrading enzymes from a dHL-60 neutrophil model in the presence of anti-inflammatory stimuli (TGF-ß, IL-4, IL-4 +IL-13). We hypothesized that Manuka honey would reduce the output of pro-inflammatory signals and increase the release of anti-inflammatory signals. The results of this study indicate that 0.5% honey significantly increases the release of CXCL8/IL-8, CCL2/MCP-1, CCL4/MIP-1ß, CCL20/MIP-3α, IL-4, IL-1ra, and FGF-13 while reducing Proteinase 3 release in the anti-inflammatory-stimulated models. However, 3% honey significantly increased the release of TNF-α and CXCL8/IL-8 while reducing the release of all other analytes. We replicated a subset of the most notable findings in primary human neutrophils, and the consistent results indicate that the HL-60 data are relevant to the performance of primary cells. These findings demonstrate the variable effects of Manuka honey on the release of cytokines, chemokines, and matrix-degrading enzymes of this model of neutrophil anti-inflammatory activity. This study reinforces the importance of tailoring the concentration of Manuka honey in a wound or tissue template to elicit the desired effects during the inflammation-resolving phase of wound healing. Future in vivo investigation should be undertaken to translate these results to a physiologically-relevant wound environment.

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

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-1ß, MIP-1α, MIP-1ß, 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.