title: Ferrous ferric chloride downregulates the inflammatory response to Rhodococcus aurantiacus infection in mice.
abstract: The healthy drink Pairogen is mainly composed of ferrous ferric chloride water that reportedly changes the status of intracellular water from oxidative to antioxidative. Here, we investigated whether Pairogen affects host immune function in a murine model of granulomatous inflammation in response to Rhodococcus aurantiacus (R. aurantiacus) infection. Longitudinal ingestion of Pairogen markedly improved the survival of infected mice in a concentration-dependent manner. Compared to mice received water, mice that ingested 10-fold-diluted Pairogen displayed rapid bacterial elimination, decreased production of tumor necrosis factor (TNF)-α and interleukin (IL)-6, and high levels of IL-10 in organs during the initial phase of infection. Moreover, histological studies showed significant reduction in the number and size of granulomas as well as amelioration of oxidative stress in the livers of mice ingested 10-fold-diluted Pairogen at 14 d post-infection. These characteristics were further pronounced in first-generation (F1) mice that also ingested 10-fold-diluted Pairogen. Following stimulation with heat-killed R. aurantiacus, the production of TNF-α, IL-6, and IL-10 by macrophages from F1 mice was similar to that detected in vivo, while their gene expression levels in these cells were significantly lower than the levels in macrophages from mice received water. Heat-killed R. aurantiacus also induced the expression of heme oxygenase-1 mRNA in the cells from F1 mice. Taken together, these results indicate that Pairogen contributes to the negative regulation of the immuno-inflammatory response to R. aurantiacus infection in mice by modulating the cellular redox state. Longitudinal ingestion of Pairogen further enhances the defense function in mouse progeny.
authors.affiliation: Department of Advanced Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan. yimin@med.hokudai.ac.jp
authors.lastname: Yimin
authors.forename: Huirong
authors.initials: H
authors.lastname: Tao
authors.forename: Masashi
authors.initials: M
authors.lastname: Kohanawa
authors.forename: Songji
authors.initials: S
authors.lastname: Zhao
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
mesh_terms: D000193:Actinomycetales Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D056704:Adaptive Immunity / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001628:Beverages; D002712:Chlorides / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D005296:Ferrous Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects; D006099:Granuloma / Q000517:prevention & control; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D012240:Rhodococcus; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002712:Chlorides; D005290:Ferric Compounds; D005296:Ferrous Compounds; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D051547:Heme Oxygenase-1; C029451:ferrous chloride; C024555:ferric chloride