A 5.8-kDa component of manuka honey stimulates immune cells via TLR4

Abstract

Honey is used as a therapy to aid wound healing. Previous data indicate that honey can stimulate cytokine production from human monocytes. The present study further examines this phenomenon in manuka honey. As inflammatory cytokine production in innate immune cells is classically mediated by pattern recognition receptors in response to microorganisms, bacterial contamination of honey and the effect of blocking TLR2 and -4 on stimulatory activity were assessed. No vegetative bacteria were isolated from honey; however, bacterial spores were cultured from one-third of samples, and low levels of LPS were detected. Blocking TLR4 but not TLR2 inhibited honey-stimulated cytokine production significantly. Cytokine production did not correlate with LPS levels in honey and was not inhibited by polymyxin B. Further, the activity was reduced significantly following heat treatment, indicating that component(s) other than LPS are responsible for the stimulatory activity of manuka honey. To identify the component responsible for inducing cytokine production, honey was separated by molecular weight using microcon centrifugal filtration and fractions assessed for stimulatory activity. The active fraction was analyzed by MALDI-TOF mass spectroscopy, which demonstrated the presence of a number of components of varying molecular weights. Additional fractionation using miniaturized, reverse-phase solid-phase extraction resulted in the isolation of a 5.8-kDa component, which stimulated production of TNF-alpha via TLR4. These findings reveal mechanisms and components involved in honey stimulation of cytokine induction and could potentially lead to the development of novel therapeutics to improve wound healing for patients with acute and chronic wounds.

Honey can prevent epidural fibrosis development after laminectomy: an experimental study

“…An acidic environment, antioxidant effects, antiinflammatory effects, antibacterial properties and immunemodulator effects enable more rapid and adequate wound healing (7). Tonks et al found in their study that the 5.8 kDa component of MH stimulates the TNF α production in macrophages through the toll-like receptor (21,22,23). It was…”

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“…It has been reported that Manuka honey increased IL-1beta, IL-6, and TNF-alpha production from Mono Mac6 cells or human monocytes [71,72], and the active component was 5.8 kDa, which increased production of these cytokines via TLR4 [73]. In addition, it was reported that oral intake of honey augmented antibody productions in primary and secondary immune responses against thymus-dependent and thymusindependent antigens [74].…”

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