Changes in gene expression induced by Micro-Immunotherapy
Keywords:Metabolic syndrome, Gene expression, Micro-arrays, Micro-immunotherapy, 2LÃƒâ€šÃ‚Â®INFLAM
AbstractBackground: Metabolic syndrome (MS) is a metabolic disorder associated with obesity, type-II diabetes, and ÃƒÂ¢Ã¢â€šÂ¬Ã…â€œlow grade inflammationÃƒÂ¢Ã¢â€šÂ¬Ã‚Â, with the concomitant increased risk of cardiovascular events. As a chronic inflammatory process, MS results in a dysregulation of the cytokine profile. 2LÃƒâ€šÃ‚Â®INFLAM, a Micro-immunotherapy (MI) medication formulated with highly diluted cytokines, is currently prescribed in Belgium for inflammatory diseases and potentially may be helpful for MS patients. Aims: To investigate the impact of 2LÃƒâ€šÃ‚Â®INFLAM on selected gene expression markers (mRNA) in patients suffering from MS, in addition to biological and clinical parameters. Methodology: Four well characterized MS adult patients with stabilized body-weight were advised to take one capsule of 2LÃƒâ€šÃ‚Â®INFLAM per day (by sublingual-oral route) for 6 months (composition in table 1). Concomitantly to biological and clinical examination, genes expression status was assessed by a DNA microarray technology (OxygenÃƒÂ¢Ã¢â‚¬Å¾Ã‚Â¢) comprising 200 genes involved mainly in oxidative stress and inflammation. Whole blood collection was performed before and after treatment (3-6 months) and mRNA levels measured. Gene expression was classified in 3 series (normally expressed, up or down-regulated) and genes related to diabetes predisposition were scored by using a proprietary Diascore (Probiox). Results: Before MI medication, a significant percentage of dysregulated genes (median: 16.3%) as well as a positive Diascore (median: 1.6) were noticed. Impressive correction of dysregulated genes (reaching 90% for one patient) was observed after 3 months of treatment (median: 2.3%) in addition to an improvement of Diascore in 3 MS patients out of 4 (median: 0.5). During the same period, both clinical and biological parameters remained unchanged. Conclusions: MS patients showing a high level of gene dysregulation efficiently normalized after 3 months of 2LÃƒâ€šÃ‚Â®INFLAM (64%-90%), suggesting a biological regulatory effect of MI and a potential benefit of this medication for diabetic patients. Up and down-deregulated gene profiles were specific for each patient and not related to cytokine components of the formula. These preliminary data support the ÃƒÂ¢Ã¢â€šÂ¬Ã…â€œdomino effectÃƒÂ¢Ã¢â€šÂ¬Ã‚Â of MI sequential formula to restore in depth the immune homeostasis. DNA microarray technology may represent a promising tool for new provings as well as for biochemical comprehension of the ÃƒÂ¢Ã¢â€šÂ¬Ã…â€œin vivoÃƒÂ¢Ã¢â€šÂ¬Ã‚Â effectiveness of highly diluted immune messengers. Table 1: 2LÃƒâ€šÃ‚Â®INFLAM composition Compounds Dilutions Interleukin-1 (IL-1): 17 CH* Interleukin-1 Ra (IL-1 Ra): 3 CH Interleukin-2 (IL-2): 9 CH Interleukin-4 (IL-4): 7 CH Interleukin-6 (IL-6): 9 CH Interleukin-8 (IL-8): 9 CH Interleukin-10 (IL-10): 4 CH Interleukin-13 (IL-13): 9 CH Ciliary Neuro Trophic Factor (CNTF): 17 CH Leukemia Inhibitory Factor (LIF): 17 CH Oncostatine M (OSM): 9 CH Platelet Derived Growth Factor (PDGF): 5 CH Prostaglandine E2 (PgE2): 200 K** Rantes (Rantes): 17 CH Transforming Growth Factor beta(TGFÃƒÅ½Ã‚Â²): 5 CH Tumor Necrosis Factor ÃƒÅ½Ã‚Â± (TNFÃƒÅ½Ã‚Â±): 17 CH SNA INFLAMa-01 18 C SNA INFLAMb-01 18 CH * CH: Centesimal Hahnemannian (1/100) ** K: Centesimal Korsakovian (1/100)
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