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Manuka honey (MH) is a type of honey known for its various therapeutic properties, including wound healing, antimicrobial activity, antioxidant effects, and anti-tumor properties. However, there is conflicting evidence regarding the role of MH in inflammatory responses, with some studies suggesting it has pro-inflammatory effects while others show predominantly anti-inflammatory activity. In this article, we aim to characterize the immunomodulatory capacity of MH using both in vitro and in vivo approaches and explore the underlying mechanisms.
The Immunomodulatory Capacity of Manuka Honey
To investigate the immunomodulatory effects of MH, we conducted experiments using macrophages and mice. In our in vitro study, we treated RAW 264.7 macrophages with 1% MH and observed a significant increase in the gene expression and secretion of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine. We also found an increase in the gene expression of other inflammatory cytokines and chemokines. These findings suggest that MH has the ability to stimulate an inflammatory response in macrophages.
In our in vivo study, we administered MH intraperitoneally to C57BL/6 mice and observed a significant increase in the number of peritoneal exudate cells (PECs), mainly due to a 35-fold increase in the recruitment of neutrophils. Importantly, this response was observed in toll-like receptor 4 (TLR4)-defective mice, indicating that the stimulatory effect of MH occurs independently of TLR4 and is unlikely to be mediated by any lipopolysaccharide (LPS) contaminant. MH administration also led to changes in the phenotypic expression and functional maturation of peritoneal macrophages, with a shift towards a specific phenotype and an increase in the expression of major histocompatibility complex (MHC) class II proteins.
Role of MyD88 in the Immunomodulatory Effects of Manuka Honey
To further understand the mechanism underlying the immunomodulatory effects of MH, we investigated the role of myeloid differentiation primary response 88 (MyD88), a critical adaptor protein in most TLR signaling pathways. We found that the MH-induced peritoneal response was largely abrogated in mice deficient in MyD88 protein, suggesting that the immunostimulatory properties of MH are dependent on MyD88-dependent signaling pathways.
Manuka Honey as an Immunomodulatory Agent in Preclinical Models
In addition to our studies, previous research has also demonstrated the immunomodulatory effects of MH in preclinical models. For example, a study showed that pretreatment with MH ameliorated tissue damage in an acute gastric ulcer model, which was correlated with increased levels of mucosal antioxidants and a reduction in pro-inflammatory cytokines. Another study found that oral administration of MH reduced tumor growth in breast cancer-bearing rats and increased the serum levels of the pro-inflammatory cytokine interferon-gamma (IFN-γ), indicating an immunomodulatory anti-tumor effect.
Potential Mechanisms of Action of Manuka Honey
The specific active ingredients in MH responsible for its immunomodulatory effects are still unclear. However, several components of MH, including methylglyoxal (MGO), dihydroxyacetone, and leptosperin, have been suggested to contribute to its activity. The Unique Manuka Factor (UMF) grading system evaluates the purity and quality of MH based on the presence of these natural components.
Conclusion
In conclusion, our study provides further evidence for the immunomodulatory properties of MH and highlights the potential utility of MH as an immunomodulatory agent in various disorders. The stimulatory effects of MH on inflammatory responses in macrophages and the recruitment of immune cells in vivo are dependent on MyD88-dependent signaling pathways. These findings contribute to a better understanding of the immunomodulatory effects of MH and support its potential use as a natural alternative for boosting immune responses.
