Comparison of in vivo immunomodulatory effects of 5-hydroxymethylfurfural and 5, 5′-oxydimethylenebis (2-furfural)

- 5-HMF stimulated productions of IgG2a and IFN-γ in response to TNP-OVA.
- 5-HMF provide a co-stimulatory signal to elicit a typical type-1 PLN response.
- OMBF elevated productions of IgG1, IgG2, IL-4 and IFN-γ to TNP-Ficoll and TNP-OVA.
- OMBF provide a neo-epitope to evoke a mixed type-1 and type-2 PLN response.
- 5-HMF and OMBF have immunosensitizing potential and represent safety concerns.

The standard of 5-Hydroxymethylfurfural (5-HMF) existed in dextrose injection as an inevitable by-product during high-temperature setrilization has been included in pharmacopoeias considering its hazardous effects on human health. We found that the concentrations of 5-HMF in some traditional Chinese medicine injections (TCMIs) far exceeded its limit in dextrose injection. Besides, we detected 5, 5′-Oxydimethylenebis (2-furfural) (OMBF) in those TCMIs containing high concentrations of 5-HMF. We investigated the in vivo immunomodulatory effects of 5-HMF and OMBF at three dose levels using the reporter antigen popliteal lymph node assay (RA-PLNA), which allows the straightforward examination and mechanistic study of immunotoxicity of low molecular weight compounds. We found that 5-HMF increased the production of IgG2a and IFN-γ when co-injected with TNP-OVA, indicating its capability of providing a co-stimulatory signal to evoke a typical type-1 immune response. Compared with the 5-HMF, OMBF elevated the production of IgG1, IgG2, IL-4 and IFN-γ in response to both reporter antigens, suggesting that OMBF can act as a neo-antigen or neo-epitope to elicit a mixed type-1 and type-2 immune response. It indicates that both 5-HMF and OMBF have immunosensitizing potential with different mechanisms, and exposure to 5-HMF and OMBF may represent a safety concern for humans.