Fitness Shifts the Balance of BDNF and IL-6 from Inflammation to Repair among People with Progressive Multiple Sclerosis.

Physical sedentarism is linked to elevated levels of circulating cytokines, whereas exercise upregulates growth-promoting proteins such as brain-derived neurotrophic factor (BDNF). The shift towards a 'repair' phenotype could protect against neurodegeneration, especially in diseases such as multiple sclerosis (MS). We investigated whether having higher fitness or participating in an acute bout of maximal exercise would shift the balance of BDNF and interleukin-6 (IL-6) in serum samples of people with progressive MS (n = 14), compared to matched controls (n = 8). Participants performed a maximal graded exercise test on a recumbent stepper, and blood samples were collected at rest and after the test. We assessed walking speed, fatigue, and maximal oxygen consumption (V·O2max). People with MS achieved about 50% lower V·O2max (p = 0.003) than controls. At rest, there were no differences in BDNF between MS and controls; however, IL-6 was significantly higher in MS. Higher V·O2max was associated with a shift in BDNF/IL-6 ratio from inflammation to repair (R = 0.7, p = 0.001) when considering both groups together. In the MS group, greater ability to upregulate BDNF was associated with faster walking speed and lower vitality. We present evidence that higher fitness indicates a shift in the balance of blood biomarkers towards a repair phenotype in progressive MS.

Differential Expression of Woodchuck Toll-Like Receptors 1-10 in Distinct Forms of Infection and Stages of Hepatitis in Experimental Hepatitis B Virus Infection.

Woodchucks infected with woodchuck hepatitis virus (WHV) represent a highly valuable model of human hepatitis B virus (HBV) infection, chronic hepatitis (CH), and virus induced-primary liver cancer. Toll-like receptors (TLRs) are important mediators of immune responses playing pivotal roles in the pathogenesis of viral diseases; however, their expression profiles in different forms of infection and stages of hepatitis, and in healthy animals remain essentially unknown. In this study, woodchuck TLRs 1-10 exon fragments were identified and TLR genes transcription quantified in livers, primary hepatocytes, peripheral blood mononuclear cells (PBMC), and in selected organs during experimental WHV infection. Among others, liver biopsies from acute hepatitis (AH) and CH showed significantly augmented expression of the majority of TLRs when compared to healthy and woodchucks prior to AH, with resolved AH or primary occult infection. In contrast to the liver tissue, significant upregulation of TLR3, TLR4, and TLR10, but downregulation of TLR7, characterized hepatocytes derived from livers of animals with resolved AH accompanied by secondary occult infection. Hepatocytes from CH showed significantly lower expression or a trend toward suppression of several TLRs when compared to hepatocytes from healthy animals and woodchucks with other forms of infection or hepatitis, suggesting that hepatocyte innate immune response is downregulated during CH. Contrastingly, upregulated transcription of some TLRs characterized PBMC throughout CH. Our study uncovered that TLR expression significantly varies between different forms of hepadnaviral infection and whether infection is accompanied or not by hepatitis. The results showed that the profiles of TLRs' expression in circulating lymphomononuclear cells do not mirror accurately those of livers and hepatocytes from infected animals. These findings are of importance to the understanding of immune process operating at different sites targeted by virus in the course of hepadnaviral infection and evaluation of future therapies modifying antiviral innate responses in the woodchuck model.