Changes in gene expression induced by Micro-Immunotherapy
Background: Metabolic syndrome (MS) is a metabolic disorder associated with obesity, type-II diabetes, and “low grade inflammationâ€ÂÂ, with the concomitant increased risk of cardiovascular events. As a chronic inflammatory process, MS results in a dysregulation of the cytokine profile. 2L®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 2L®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 2L®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 (Oxygenâ„¢) 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 2L®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 “domino effect†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 “in vivo†effectiveness of highly diluted immune messengers. Table 1: 2L®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(TGFβ): 5 CH Tumor Necrosis Factor α (TNFα): 17 CH SNA INFLAMa-01 18 C SNA INFLAMb-01 18 CH * CH: Centesimal Hahnemannian (1/100) ** K: Centesimal Korsakovian (1/100)