Variations of IL2, IL6, TNF alpha plasmatic levels in relapsing remitting multiple sclerosis

We performed a longitudinal analysis of serum IL2, IL6 and TNF alpha concentrations in 40 relapsing remitting MS patients and 20 healthy subjects. Disease activity was quantified by Minimal Record of Disease (M. R. D.) for MS, every 2 or 3 months. IL2, IL6, TNF alpha production was analysed without and with PHA stimulation of whole blood for 2 hours at 37 degrees C. No significant change in IL2 level was found in MS serum. Individual TNF alpha production was significantly increased (P < 0.007) during relapses. The global spontaneous IL6 production was markedly higher in the relapse group than in the control group (p < 0.01) and than in the remission group (P < 0.002) without significant individual variations of cytokine levels regarding the disease activity. Productions of cytokines were enhanced by PHA stimulation, a condition that however suppressed the differences observed without mitogen stimulation. Our data suggest that TNF alpha could be a marker for relapses while IL6 might reflect the global activity of the immune system in MS

Identification of genetic elements in metabolism by high-throughput mouse phenotyping

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome