Benign Multiple Sclerosis Is Characterized by a Stable Neuroimmunologic Network

Abstract

Objectives: Patients diagnosed with multiple sclerosis (MS) but without disability (Expanded Disability Status Scale score <2) form a specific group within those patients suffering from relapsing-remitting MS. Several neuroimmunologic effectors, including cytokines and melatonin, are known for their influence on the initiation of relapses and progression of the disease. Methods: We evaluated 41 female patients with benign MS with respect to their clinical course, treatments and neuroimmunological parameters, including cytokines and melatonin. One subgroup was followed up for 7 years, and another group was evaluated during acute clinical relapse. Results: The benign MS course in this homogeneous group of young patients was demonstrated by mild disease progression in 16% over 7 years. Initially, patients treated with azathioprine (AZA) revealed significantly reduced melatonin serum levels (p = 0.04) compared to untreated patients, but not at follow-up. During acute relapse, treatment with corticosteroids (CS) resulted in increased levels of type 2 cytokines as well as reduced type 1 cytokine levels. Conclusions: Our study supports the functional role of CS acting as an antiinflammatory protagonist during MS relapse, by inducing a shift towards predominance of type 2 cytokines. AZA showed a more subtle modulation of immune functions, reflected by reduced levels of the immune active hormone melatonin. During follow-up, it became apparent that stabilized levels of the interacting Th1/Th2-derived cytokines and melatonin are maintained in concordance with the benign course of MS. These findings are in accordance with the hypothesis that benign MS is characterized by a balanced cytokine and neuroendocrine network, which is supported by immune-modulating therapies.

Serum levels of melatonin and cytokines in multiple sclerosis

“…[7] However, Haas et al, emphasize the high level of melatonin in this disease and suggest that melatonin is an initiating factor in disease progression and attack. [8] Several factors impair the production of melatonin, including seasonal affective disorder. [9] On the other hand, findings of a study suggest that patients with affective disorder are at higher risk for MS-associated cognitive dysfunction and neuropsychiatric symptoms, a conclusion that has implications for the emerging role of personality in clinical neuroscience.…”

Cytokine responses to acute and chronic exercise in multiple sclerosis

“…These findings suggest that individuals with MS may respond to physical stress similarly to matched healthy controls. In fact, stabilized levels of interacting Th1/ Th2 cytokines are maintained in the benign course of MS, and it is hypothesized that benign MS (EDSS Ͻ 2) is characterized by a fairly balanced cytokine and neuroendocrine network (16). Perhaps MS subjects with higher disability (EDSS Ͼ 5) may exhibit a different response due to a stronger immune dysregulation.…”

Effects of cytokines on microglial phenotypes and astroglial coupling in an inflammatory coculture model

“…Although it is well known that cytokines take part in multiple effector mechanisms of the inflammatory cascade in the central nervous system (CNS), our knowledge as to their mechanistic role is poorly understood. For instance, increased levels of cytokines have been detected in multiple sclerosis (MS) lesions, cerebrospinal fluid (CSF), and serum bloods of MS patients, including interleukins (IL-1 and IL-6), interferon-g (IFN-g), tumor necrosis factor-a (TNF-a), and throughout transforming growth factor-b (TGF-b) (Merill and Benveniste, 1996;Haase and Faustmann, 2004). Even though application of the antiinflammatory cytokine interferon-b (IFN-b) comprises a common therapeutic regimen in the treatment of MS patients, a profound knowledge on its mechanistic background is not available (for review, see McCormack and Scott, 2004).…”