Interferon ß-1a reduces increased interleukin-16 levels in multiple sclerosis patients.

OBJECTIVES: There is convergent evidence for an important role of interleukin-16 (IL-16) in the pathogenesis of multiple sclerosis (MS). IL-16 serves as a chemoattractant for different immune cells that are involved in developing lesions. Here, we compared IL-16 levels of MS patients and controls and addressed the long-term effect of IFN-ß, the most common immunomodulatory MS therapy, on IL-16 serum levels in MS patients over 2 years. Beyond this, we analysed the expression of IL-16 in two CD4(+) T-cell subsets, Th1 and Th17 cells, which are important autoimmune mediators and affected by IFN-ß treatment, derived from myelin-specific T-cell transgenic mice. MATERIALS AND METHODS: IL-16 serum levels of 17 controls and of 16 MS patients before therapy and at months 1, 2, 3, 6, 9, 12 and 24 during IFN-ß1a therapy were determined by ELISA. MRI was performed before therapy, at months 12 and 24. IL-16 expression of in vitro differentiated murine myelin oligodendrocyte glycoprotein (MOG)-specific Th1 and Th17 cells was quantified by real-time PCR. RESULTS: Before therapy, MS patients showed significantly elevated IL-16 levels compared with controls irrespective of disease activity determined by MRI. Therapy with IFN-ß1a led to a significant linear decrease in IL-16 serum levels beginning after 2 months. MOG-specific Th17 cells expressed more IL-16 than Th1 cells. CONCLUSIONS: Reduction in increased IL-16 levels may be of relevance for the therapeutic effect of IFN-ß1a in MS. Easily accessible IL-16 serum levels hold a potential as biomarker of treatment efficacy in MS.

Analysis of the immune response to Neospora caninum in a model of intragastric infection in mice.

To study experimental Neospora caninum infection initiated at the gastrointestinal tract, Toll-like Receptor 4- and functional IL-12Rbeta2 chain-deficient C57BL/10 ScCr mice were challenged intragastrically with 5 x 10(6) N. caninum tachyzoites. All parasite-inoculated mice eventually died with disseminated infection. In contrast, immunocompetent BALB/c mice challenged with 1 x 10(7) N. caninum tachyzoites by the intragastric (i.g.) or the intraperitoneal (i.p.) route remained alive for at least 6 months. Expansion of splenic B- and T-cells, the latter displaying both activated and regulatory phenotypes, and increased levels of IFN-gamma and IL-10 mRNA were detected in both groups of infected BALB/c mice compared with non-infected controls, whereas in the Peyer's patches only IFN-gamma mRNA levels were found to be increased. Parasite-specific IgG1, IgG2a and IgA antibody levels were elevated in the sera of all infected mice, whereas increased N. caninum-specific IgA levels were detected in intestinal lavage fluids of i.g. challenged mice only. These results show that N. caninum infection can be successfully established in mice by i.g. administration of tachyzoites. They also show that the immune response elicited in i.g. or i.p. infected BALB/c mice, although conferring some degree of protection, was not sufficient for complete parasite clearance.