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
See also VitaminDWiki
- Chemotherapy might be amplified by vitamin D
- Breast cancer chemotherapy benefits from highest vitamin D levels – June 2014
- Cancer Chemotherapy and vitamin D – Review March 2013
- Mustard gas survival greatly improved by Vitamin D (mice) March 2016
See also web
“Mustargen, mustine and mechlorethamine hydrochloride are all forms of nitrogen mustard”
“Nitrogen mustard drugs are extremely toxic. In fact, they can actually cause cancer as well as help cure it.”
Download the PDF from VitaminDWiki
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.