Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system. An impaired hypothalamo-pituitary axis (HPA) and stress reactivity have extensively been discussed without convincing expertimental evidence. We choose a standardized acute psychological stressor to determine whether MS patients show altered endocrine and immune responses to stress. In the preliminary analysis we included 14 relapsing-remitting MS patients and 5 healthy controls. During exposure to the stress we saw a reduced ACTH response in MS patients. IL-6, IL-6 receptor did not differ between stressed and non-stressed MS patients. TNF-alpha after whole blood stimulation revealed a reduced capacity in 5 stressed versus 7 control MS patients. From these data we postulate an altered neural-- immune signaling in relapsing-remitting MS patients during acute experimental stress with an HP A hyporeactivity and a TNF hyporesponsiveness. But results have to be confirmed in a larger patient sample.
Key words: stress, multiple sclerosis, immune response, endocrine response.
Multiple sclerosis (MS) is the most frequent disabling disease of young adults. In the beginning stages of the disease it is very difficult to predict whether the course will be rapidly progressive or relapsing-remitting. The target of the pathophysiological process is the myelin layer of nerve axons in the central nervous system (CNS). Pathomorphologically, MS is characterized by multiple demyelinating plaques with a differing extent of inflammatory cells. An autoimmune process is the generally accepted underlying etiology. Genetical, immunological and environmental factors are involved in the manifestation of the disease. Furthermore, neuroendocrinological factors are discussed, but the scientific evidence is inconsistent. As in many other chronic diseases, psychological factors are regarded important in the course of the disease, especially concerning manifestation and relapses. The evidence for a stress-mediated activation of autoimmunity nevertheless is weak.
Immunology of MS
MS is regarded a predominantly T-cell-mediated, demyelinating process in the CNS. An unknown environmental antigen is thought to elicit the inflammatory cascade (Hartung and Giovannoni, 1996). Via molecular mimicry, physiological autoaggressive T-cells might be activated through this environmental antigen, leading to the cascade of inflammatory reaction. Different authors have shown some association of MS to human leucocyte antigens (HLA) and T-cell receptor repertoires (Ransohoff et al., 1995). Sibling studies have shown an increased risk for MS when family members are already affected. Thus there is evidence for a genetic component in the disease. A quite specific humoral immune response can be detected in the cerebrospinal fluid (CSF) which suggests B-cell activation as a further pathogenetic factor (Tourtellotte, 1985). During the last 3 years, elevated levels of different cell adhesion molecules (E-selectine, intracellular-adhesion-molecules I and 3, vascular-cell adhesion-molecule 1) and cytokines (tumor-necrosis-factor-alpha and its soluble receptor, interferon-gamma, transforming growth factor beta, interleukins 2, 4, 10, 12) could be detected in tissue, CSF and serum of MS patients (Arnason et al., 1995; Hartung and Giovannoni ,1996; Rieckmann et al., 1994; Sharief et al., 1993; Trotter et al., 1991).
For many years, any attempt to establish CSF or serum activity factors for MS failed. Today there is first evidence of an association between cytokines and adhesion molecules and the disease activity (Rieckmann et al., 1994 and 1997; Sahrief et al., 1993). Perhaps these parameters have a prognostic relevance. The first approved MS therapy is itself a cytokine, interferon-Beta (The Interferon-Beta Multiple Sclerosis Study Group, 1995). A major mechanism of interferon-Beta-activity might be the modulation of interferon-gamma and tumornecrosis-factor-alpha mitigated immune alterations. …