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

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.

Nonenzymatic glycation of immunoglobulins leads to an impairment of immunoreactivity.

Incubation of purified human and rabbit immunoglobulin G with glucose leads to covalent incorporation of the sugar into the protein, depending on glucose concentration, incubation time and pH. Furthermore, the level of glycated immunoglobulin G from normal and diabetic subjects has been determined using the thiobarbituric acid reaction. The median for glycated immunoglobulin G, expressed as mmol 5-hydroxymethylfurfural per mol IgG, obtained from 20 normal and 29 diabetic subjects was 62 and 107, respectively. Glucose incubation of immunoglobulin G purified from rabbit anti-human-transferrin serum, from human anti-varicella/zoster virus serum and from human anti-lues-spirochete serum, respectively, leads to a marked decrease in biological activity, as determined in a micro complement fixation test. Inactivation of specific antibody was dependent on incubation time and glucose concentration employed. Loss in complement-fixing activity was observed at glycation levels well comparable to those found in diabetics.