Multiple sclerosis (MS) is an autoimmune disease that results in demyelination of axonal tracts in the CNS causing a wide range of neurological symptoms [1]. Major histocompatibility (MHC) class II-restricted CD4+ T-cells that recognize CNS components are the predominant pathogenic mediators in MS and act by secreting inflammatory cytokines such as IFN-γ. Epidemiological studies suggest that unidentified environmental factors contribute to the etiology of MS [2,3] and diet is a commonly postulated factor because strong associations have been observed between increased MS prevalence and diets high in meat and dairy products and low in fish [1,4-6].
These epidemiological findings have provided a rationale for a number of clinical trials aimed to establish beneficial effect of dietary interventions in MS, with heterogeneous results [1]. There have been reports indicating that a diet with a very low saturated fat content may provide long term benefits for rates of mortality, relapse severity and disability in MS, particularly if initiated during the earliest stages of the disease [7,8].
While the nature of the event(s) in MS that lead to activation and proliferation of T-cells is unknown, a similar disease can be induced in rodents by subcutaneous (s.c.) injection of either spinal cord homogenate (SCH) or CNS antigens including myelin basic protein, myelin oligodendrocyte glycoprotein, or proteolipid protein; or phenotypic peptides of these [9]. Besides different triggering mechanisms, experimental allergic encephalomyelitis (EAE) animal models share many characteristics of MS [10]. This includes an "activation phase" where antigen-presenting cells process the immunized antigen, migrate to the lymph nodes and present immunodominant peptides to naïve T-cells; and an "effector phase" where CD4+ T-cells that recognize antigen proliferate and cross the blood-brain barrier to lead an inflammatory attack that results in demyelinated lesions. In most models, the T helper 1 (Th1) subset of T-cells has been implicated in the induction of EAE.
In a previous study [11] we reported the inhibitory effect of a severe caloric restriction (i.e., a 66 % reduction of calorie intake) on the development of EAE in Lewis rats. Calorie-restricted rats did not exhibit the augmented lymph node mitogenic response to concanavalin A (Con A) following SCH immunization found in controls, nor the increase in plasma ACTH and corticosterone found after SCH immunization [11].
The present study was carried out to further examine the immune responses after EAE in rats subjected to a severe (i.e., 66 %) or a moderate (i.e. 33 %) calorie restriction. The mitogenic responses and lymphocyte subset groups of spleen, submaxillary lymph node (SmLN) and thymus were assessed. The changes in immune parameters were correlated with the release of interferon (IFN)-γ in vitro by immunocompetent cells.
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