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Chemo drug (Nitrogen Mustard in this study) side effects minimized by vitamin D (mice) – March 2015

Suppression of Hyperactive Immune Responses Protects against Nitrogen Mustard Injury.

J Invest Dermatol. 2015 Dec;135(12):2971-81. doi: 10.1038/jid.2015.322. Epub 2015 Aug 19.

  • Nitrogen Mustard was the first Chemotherapy Drug (based on WWI mustard gas) 1 atom different
  • Nitrogen Mustard is still being used for
    Leukemia, Lymphoma, Hodgkin's disease, Lung cancer, Breast cancer
  • Nitrogen Mustard has major side effects (but not everyone gets ALL of them)
    Nausea and vomiting, Hair loss, Mouth sores, Darkening of veins, Loss of fertility
  • This study shows that Vitamin D reduces side effects in mice
  • Previous studies have shown that many chemo doses can be reduced 3X with Vitamin D

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Au L1,2, Meisch JP1, Das LM1, Binko AM1, Boxer RS3, Wen AM4, Steinmetz NF4,5,6,7, Lu KQ1.
1Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
2Department of Chemical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
3Department of Medicine, University of Colorado School of Medicine, Denver, Colorado, USA.
4Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
5Department of Radiology, Case Western Reserve University, Cleveland, Ohio, USA.
6Department of Material Science and Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
7Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio, USA.

DNA alkylating agents like nitrogen mustard (NM) are easily absorbed through the skin and exposure to such agents manifest not only in direct cellular death but also in triggering inflammation. We show that toxicity resulting from topical mustard exposure is mediated in part by initiating exaggerated host innate immune responses. Using an experimental model of skin exposure to NM we observe activation of inflammatory dermal macrophages that exacerbate local tissue damage in an inducible nitric oxide synthase (iNOS)-dependent manner. Subsequently these activated dermal macrophages reappear in the bone marrow to aid in disruption of hematopoiesis and contribute ultimately to mortality in an experimental mouse model of topical NM exposure. Intervention with a single dose of 25-hydroxyvitamin D3 (25(OH)D) is capable of suppressing macrophage-mediated iNOS production resulting in mitigation of local skin destruction, enhanced tissue repair, protection from marrow depletion, and rescue from severe precipitous wasting. These protective effects are recapitulated experimentally using pharmacological inhibitors of iNOS or by compounds that locally deplete skin macrophages. Taken together, these data highlight a critical unappreciated role of the host innate immune system in exacerbating injury following exposure to NM and support the translation of 25(OH)D in the therapeutic use against these chemical agents.

PMID: 26288355

Attached files

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6450 Nitrogen mustard.compressed.pdf admin 03 Mar, 2016 968.72 Kb 943
6449 Mustard.jpg admin 03 Mar, 2016 7.88 Kb 1185
6448 Nitrogen mustard survival.jpg admin 03 Mar, 2016 23.05 Kb 1052