Question:

I suspect the sale of diesel cars to MS folks will dramatically increase. Jack N Dalton P.S. There comes a time when further intense research can become counterproductive. 1: Brain. 2003 Sep 23 [Epub ahead of print]. Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis. Bar-Or A, Nuttall RK, Duddy M, Alter A, Kim HJ, Ifergan I, Pennington CJ, Bourgoin P, Edwards DR, Yong VW. Montreal Neurological Institute, Montreal, Quebec, Canada. Matrix metalloproteinases (MMPs) are implicated in multiple sclerosis where one of their roles may be to facilitate the transmigration of circulating leukocytes into the CNS. Studies have focused on only a few MMPs, and much remains unknown of which of the 23 MMP family members is/are critical to the multiple sclerosis disease process. Using quantitative real time polymerase chain reactions, we have systematically analysed the expression of all 23 MMP members in subsets of leukocytes isolated from the blood of normal individuals. We found a distinctive pattern of MMP expression in different cellular populations: MMP-11, MMP-26 and MMP-27 were enriched in B cells, while MMP-15, MMP-16, MMP-24 and MMP-28 were prominent in T lymphocytes. Of interest is the enrichment of a majority of MMP members in monocytes: MMP-1, MMP-3, MMP-9, MMP-10, MMP-14, MMP-19 and MMP-25.  MMP-2 and MMP-17 were also significantly represented in monocytes, although B cells had significant amounts of these MMPs. In correspondence with their strong expression of many MMP members, monocytes migrated more rapidly across a model of the blood-brain barrier in culture than T or B lymphocytes. Finally, we found higher levels of two of the monocyte-expressed MMPs in multiple sclerosis patients compared with normal individuals: MMP-2 and MMP-14. Tissue inhibitor of metalloproteinases (TIMP)-2 was also elevated in monocytes from multiple sclerosis patients, providing a mechanism for the reported activation of MMP-2 by MMP-14 and TIMP-2. These results emphasize that monocytes are prominent contributors of the neuroinflammation in multiple sclerosis through a mechanism that involves their high MMP expression and that they identify specific MMP members as targets for novel therapeutics in the disease. PMID: 14506071 [PubMed - as supplied by publisher] 1: Int Arch Allergy Immunol. 2003 Jul;131(3):201-8. Reduction of IL-12 p40 production in activated monocytes after exposure to diesel exhaust particles. Nilsen AM, Hagemann R, Eikas H, Egeberg K, Norkov T, Sundan A. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. BACKGROUND: A reduction of IL-12 production by lung macrophages may partly explain the presumed adjuvant effect of (DEP) in allergy and asthma. IL-12 stimulates T helper type 1 (Th1) lymphocytes, which inhibit Th2 cells via Th1-specific cytokines. The aim of this study was to investigate the influence of DEP on the production of IL-12 p40 in lipopolysaccharide (LPS)-activated monocytes. METHODS: The human monocytic cell line Mono-Mac-6 was stimulated with LPS (200 ng/ml) and grown with DEP (0-200 microg/ml) for 0, 6 or 24 h. IL-12 p40 and the pro-inflammatory cytokine TNF were analysed in the cell supernatants by ELISA and a cell assay, respectively.  RESULTS: Levels of IL-12 p40 correlated inversely with the DEP exposure concentrations, whereas TNF increased in parallel to the DEP concentrations. At a DEP concentration of 200 microg/ml, the amount of IL-12 p40 was 35% of that observed without DEP. The corresponding TNF value was 230% of the control.  Reduced viability, binding of cytokines to DEP or endotoxin in the DEP samples cannot fully explain the changes in the concentrations of these two cytokines.  CONCLUSION: DEP diesel exhaust particles seem to inhibit the production of IL-12 p40 and stimulate that of TNF in activated monocytes. This may partly explain the presumed adjuvant effect of DEP in atopy; by altering the Th1/Th2 balance via down-regulation of IL-12, the Th2 response characteristic of allergy and asthma may be favoured. Copyright 2003 S. Karger AG, Basel PMID: 12876411 [PubMed - indexed for MEDLINE]

Response:

great find on the mmparticle. sadly, mmp’s are absolutely needed to live.  going after them os only a partial answer.  attacking mmp’s will never stop ms. least not as far as i’ve been able to determine. look into epitope spread jack. that phenomenon is very much the fabric of our disease. and unlike mmp’s myelin seeking autoantibodies have no place whatsoever in our bodies. there’s a team at stanford making protein chips that recognize 500 myelin epitopes.  in  reality those chips are a solid test for ms.  a real live gold standard, "i’ll call ya tomorrow with the news", case closed lab test. not being used as such.  but you show 15-20+ myelin antibodies in your blood and my freind you gots ms. i can even tell ya why the vaccines haven’t been completely effective and how they could be made so. at least i’m pretty sure i can. ms autoimmunity is a wave propagation. regards ed "jack n dalton" <jdal…@ix.netcom.com> wrote in message <news:mF9eb.37448$[email protected]>… – Hide quoted text — Show quoted text -> I suspect the sale of diesel cars to MS folks will dramatically increase. > Jack N Dalton > P.S. There comes a time when further intense research can become > counterproductive. > 1: Brain. 2003 Sep 23 [Epub ahead of print]. > Analyses of all matrix metalloproteinase members in leukocytes emphasize > monocytes as major inflammatory mediators in multiple sclerosis. > Bar-Or A, Nuttall RK, Duddy M, Alter A, Kim HJ, Ifergan I, Pennington CJ, > Bourgoin P, Edwards DR, Yong VW. > Montreal Neurological Institute, Montreal, Quebec, Canada. > Matrix metalloproteinases (MMPs) are implicated in multiple sclerosis where > one of their roles may be to facilitate the transmigration of circulating > leukocytes into the CNS. Studies have focused on only a few MMPs, and much > remains unknown of which of the 23 MMP family members is/are critical to the > multiple sclerosis disease process. Using quantitative real time polymerase > chain reactions, we have systematically analysed the expression of all 23 > MMP members in subsets of leukocytes isolated from the blood of normal > individuals. We found a distinctive pattern of MMP expression in different > cellular populations: MMP-11, MMP-26 and MMP-27 were enriched in B cells, > while MMP-15, MMP-16, MMP-24 and MMP-28 were prominent in T lymphocytes. Of > interest is the enrichment of a majority of MMP members in monocytes: MMP-1, > MMP-3, MMP-9, MMP-10, MMP-14, MMP-19 and MMP-25.  MMP-2 and MMP-17 were also > significantly represented in monocytes, although B cells had significant > amounts of these MMPs. In correspondence with their strong expression of > many MMP members, monocytes migrated more rapidly across a model of the > blood-brain barrier in culture than T or B lymphocytes. Finally, we found > higher levels of two of the monocyte-expressed MMPs in multiple sclerosis > patients compared with normal individuals: MMP-2 and MMP-14. Tissue > inhibitor of metalloproteinases (TIMP)-2 was also elevated in monocytes from > multiple sclerosis patients, providing a mechanism for the reported > activation of MMP-2 by MMP-14 and TIMP-2. > These results emphasize that monocytes are prominent contributors of the > neuroinflammation in multiple sclerosis through a mechanism that involves > their high MMP expression and that they identify specific MMP members as > targets for novel therapeutics in the disease. > PMID: 14506071 [PubMed - as supplied by publisher] > 1: Int Arch Allergy Immunol. 2003 Jul;131(3):201-8. > Reduction of IL-12 p40 production in activated monocytes after exposure to > diesel exhaust particles. > Nilsen AM, Hagemann R, Eikas H, Egeberg K, Norkov T, Sundan A. > Department of Cancer Research and Molecular Medicine, Faculty of Medicine, > Norwegian University of Science and Technology, Trondheim, Norway. > BACKGROUND: A reduction of IL-12 production by lung macrophages may partly > explain the presumed adjuvant effect of (DEP) in allergy and asthma. IL-12 > stimulates T helper type 1 (Th1) lymphocytes, which inhibit Th2 cells via > Th1-specific cytokines. The aim of this study was to investigate the > influence of DEP on the production of IL-12 p40 in lipopolysaccharide > (LPS)-activated monocytes. METHODS: The human monocytic cell line Mono-Mac-6 > was stimulated with LPS (200 ng/ml) and grown with DEP (0-200 microg/ml) for > 0, 6 or 24 h. IL-12 p40 and the pro-inflammatory cytokine TNF were analysed > in the cell supernatants by ELISA and a cell assay, respectively.  RESULTS: > Levels of IL-12 p40 correlated inversely with the DEP exposure > concentrations, whereas TNF increased in parallel to the DEP concentrations. > At a DEP concentration of 200 microg/ml, the amount of IL-12 p40 was 35% of > that observed without DEP. The corresponding TNF value was 230% of the > control.  Reduced viability, binding of cytokines to DEP or endotoxin in the > DEP samples cannot fully explain the changes in the concentrations of these > two cytokines. >  CONCLUSION: DEP diesel exhaust particles seem to inhibit the production of > IL-12 p40 and stimulate that of TNF in activated monocytes. This may partly > explain the presumed adjuvant effect of DEP in atopy; by altering the > Th1/Th2 balance via down-regulation of IL-12, the Th2 response > characteristic of allergy and asthma may be favoured. > Copyright 2003 S. Karger AG, Basel > PMID: 12876411 [PubMed - indexed for MEDLINE]

Response:

Jack; > I suspect the sale of diesel cars to MS folks will dramatically increase.

I did not understand the complicated chemistry in this article, but I can tell you one thing: exposure to diesel fumes knocks me flat. Diesel exhaust is far worse that gasoline exhaust; I am not sure why. I’m sure there is a reason out there; all I know is what it does to me and other people. Sylvia

Response:

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