Gene expression profiles reveal homeostatic dynamics during interferon-beta therapy in multiple sclerosis

Understanding the mechanisms that sustain the effects of disease modifying drugs in multiple sclerosis (MS) may help refine current therapies and improve our knowledge of disease pathogenesis. By using cDNA microarrays, we investigated gene expression in the peripheral blood mononuclear cells (PBMC) of 7 MS patients, at baseline (T0) as well as after 1 (T1) and 3 months (T3) of interferon beta-1a (IFN-beta-1a; Rebif 44 microg) therapy. Gene expression changes involved genes of both immunological and non-immunological significance. We validated IL-10 up-regulation, which is in accordance with previous reports, and other novel changes that underscore the capacity of IFN-beta to impair antigen presentation and migration of inflammatory elements into the central nervous system (up-regulation of filamin B and down-regulation of IL-16 and rab7). Overall, gene expression changes became less pronounced after 3 months of therapy, suggesting a homeostatic response to IFN-beta. This may be of use for the design of new treatment schedules.     

Differentiation-dependent and subset-specific recruitment of T-helper cells into murine liver

It has been suggested that the liver traps and deletes activated and potentially harmful T cells, especially of the CD8(+) subset, providing mechanisms to limit systemic immune responses. It is unknown whether this also applies to CD4(+) T cells. In this study, we show that activated stages of CD4(+) T cells were trapped in the liver on intraportal injection. Intravital microscopy showed an immediate adhesion of activated CD4(+) T cells within periportal sinusoids after intraportal injection. Furthermore, we detected high frequencies of interferon gamma (IFN-gamma)-- (Th1) and interleukin 4 (IL-4)-- (Th2) synthesizing effector cells in the liver. Transfer experiments were performed to identify those phenotypes showing specific retention in the liver. Our data show that effector stages and activated cells in general are more efficiently recruited into the liver than resting CD4(+) T cells, similar to what has previously been shown for CD45RB(low) memory cells. In addition, we observed a certain preference for Th1-polarized cells to be trapped by the liver. However, the actual cytokine-producing cells did not specifically enrich among the total population. In conclusion, these data indicate that the liver acts as a filter for activated and memory/effector cells. Cells trapped in the liver might subsequently undergo modulatory influences exerted by the postulated specific microenvironment of the liver.     

Effects on work resumption of a co-operation project in vocational rehabilitation. Systematic,multi-professional,client-centred and solution-oriented co-operation

Purpose.?The present aim was to evaluate the effect of systematic multi-professional co-ordinated rehabilitation (the Stockholm Co-operation Project) on the number of days’ sick leave during the first and second half-years after the rehabilitation co-ordination period, compared to the year before. Another aim was to evaluate the economic effects at national level.

Method.?A matched-pairs design was used. The study group was based on 64 rehabilitees employed by a public employer in Stockholm, who took part in a systematic multi-professional co-operation project. To obtain pairs, the 64 individuals were individually matched with 64 people who received conventionally organised rehabilitation. Thus, there were 128 subjects altogether.

Results.?The study group had substantially less sick leave days per month than the comparison group during the second half-year after the rehabilitation co-ordination period. The effect was even greater in a subgroup with more previous sick leave. During the first half-year after the intervention the comparison group had relatively more sick leave. No effect was found for a subgroup with less previous sick leave. The economic benefit of the intervention was estimated to €1,278 per month and person based on the whole group, and to €2,405 per month and person based on those with more sick leave.

Conclusions.?People who undergo co-ordinated rehabilitation have more working days after the intervention period than those with conventional rehabilitation. This way for rehabilitation actors to co-operate gives better outcomes for rehabilitation cases with long previous sick leave, but not for cases with less previous sick leave. It also generates economic gains at several levels.     

Über die Stabilitätsreaktion des Blutes,Nebst Vergleichwerten bei Verschiedener Methodik

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