The primary effector mechanisms of the immune system leading to tissue destruction and clinical signs in EAE remain unclear. Macrophages invading the CNS and its inflammatory mediators like NO are suggested to be involved. Aged rats are resistant to the induction of the classic EAE paralysis signs when compared with the highly susceptible young rats. To test the contribution of NO on EAE pathogenesis, aged and young Wistar rats were immunized with myelin antigens in CFA and analyzed with respect to the capacity of macrophages to invade CNS and to produce NO. Demyelination degree and immunological response were also evaluated. Histological analysis of spinal cord and cerebellum showed no differences in inflammation or extent of demyelination between both age groups. The ratio between proinflammatory (CD4+IFN-¦Ã+) and anti-inflammatory (CD4+IL-4+) T-cells was lower in aged animals as assessed by flow cytometry analysis of intracellular cytokines. Enriched macrophage populations obtained by plate cell adhesion after peritoneal lavage were used to quantify NO production. Determination by Griess reaction of NO amounts showed that during EAE macrophages from aged rats are less capable to produce NO than those from young ones. It can be concluded that NO production during EAE development can play an essential role in the pathogenesis of active EAE.
The primary effector mechanisms of the immune system leading to tissue destruction and clinical signs in EAE remain unclear. Macrophages invading the CNS and its inflammatory mediators like NO are suggested to be involved. Aged rats are resistant to the induction of the classic EAE paralysis signs when compared with the highly susceptible young rats. To test the contribution of NO on EAE pathogenesis, aged and young Wistar rats were immunized with myelin antigens in CFA and analyzed with respect to the capacity of macrophages to invade CNS and to produce NO. Demyelination degree and immunological response were also evaluated. Histological analysis of spinal cord and cerebellum showed no differences in inflammation or extent of demyelination between both age groups. The ratio between proinflammatory (CD4+IFN-¦Ã+) and anti-inflammatory (CD4+IL-4+) T-cells was lower in aged animals as assessed by flow cytometry analysis of intracellular cytokines. Enriched macrophage populations obtained by plate cell adhesion after peritoneal lavage were used to quantify NO production. Determination by Griess reaction of NO amounts showed that during EAE macrophages from aged rats are less capable to produce NO than those from young ones. It can be concluded that NO production during EAE development can play an essential role in the pathogenesis of active EAE.
