title: Comparison of in vivo immunomodulatory effects of 5-hydroxymethylfurfural and 5, 5'-oxydimethylenebis (2-furfural).
abstract: 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 IgG2aand 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.
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Ni
authors.initials: N
authors.lastname: Lin
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Liu
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Qingce
authors.initials: Q
authors.lastname: Zang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Jiuming
authors.initials: J
authors.lastname: He
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Zeper
authors.initials: Z
authors.lastname: Abliz
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China; Beijing Union-Genius Pharmaceutical Technology Development Co., Ltd., Beijing 100050, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China; Beijing Union-Genius Pharmaceutical Technology Development Co., Ltd., Beijing 100050, PR China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China; Beijing Union-Genius Pharmaceutical Technology Development Co., Ltd., Beijing 100050, PR China. Electronic address: jinhongtao@imm.ac.cn.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Jin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: C000622609:5,5'-oxydimethylenebis(2-furfural); D007155:Immunologic Factors; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde
keywords: 5, 5′-Oxydimethylenebis (2-furfural); 5-Hydroxymethylfurfural; Immune-mediated hypersensitivity reaction; Immunomudulation; Immunosensitizing; Popliteal lymph node assay; Traditional Chinese medicine injection