Cytokines in multiple sclerosis: methodological aspects and pathogenic implications

Abstract

Multiple sclerosis (MS) is one of the leading causes of disability among young adults of Caucasian origin. One hundred and fifty years after the first description of the disease, the cause of MS remains unknown. Ironically, the few hypotheses concerning MS pathogenesis that are valid today were first proposed over a hundred years ago. However, equipped with the advanced technology of molecular biology and imaging systems, we are at present progressively uncovering dues to understanding the pathogenesis of the disease. It is dearly evident that aberrant immune responses occur in MS, and it is likely that the spectrum of cytokines produced decisively influences disease outcome. The detrimental consequences of IFN-gamma and the beneficial effects of IFN-beta treatment in MS support this hypothesis. However, there are still major gaps in our knowledge of the involvement of cytokines in MS. Numerous studies have addressed the question of cytokine levels in MS, often with conflicting results; elevated, normal and decreased levels of almost all cytokines have been reported. This scenario most probably reflects methodological dilemmas as well as the complex biology of cytokines. Here we focus on possible reasons for the discrepancies of results reported on cytokines in MS and summarize findings obtained in particular by the application of enzyme-linked immunospot (ELISPOT) assays to cytokine studies in MS.

Effects of Interferon β-1a and Interferon β-1b Monotherapies on Selected Serum Cytokines and Nitrite Levels in Patients with Relapsing-Remitting Multiple Sclerosis: A 3-Year Longitudinal Study

“…IFNγ and TNFα are usually deemed proinflammatory. However, there is also evidence for a double-sided ‘Janus' role of both TNFα and IFNγ in chronic autoimmune inflammation and MS [66,70,71,72], and it has been proposed that the TNFα/IL-6 balance is of importance for the therapeutic effect of the IFNβ treatments [73]. The relationship between changes in EDSS scores and IFNγ/IL-6 ratio in our study groups (compare fig.…”

Leptin and its soluble receptor in plasma of patients suffering from remitting–relapsing multiple sclerosis (MS)

“…This could be important for MS because IFN-g has been shown to be detrimental for this disease [30,31], whereas IL-10 to be beneficial [32]. In this context, the failure of leptin to induce IL-2 or IL-4 production by patients' or controls' cells can be seen as fortuitous, because IL-4 can cause anaphylaxis in general [33e35], and also anaphylaxis triggered by self-antigens in an autoimmune setting [36].…”

Tumor necrosis factor-alfa and interleukin-4 in cerbrospinal fluid and plasma in different clinical forms of multiple sclerosis

“…In so calledthe time course, most of these patients develop secondary progressive form of MSsecondary progressive MS (SPMS), while the smallest proportion of patients is characterized by the progressive course from the onset -primary progressive MS (PPMS). Some studies 7,8 suggest that different immunopathological mechanisms might be involved in the development of different MS types. That might explain different course and prognosis of the disease, necessity of different therapeutic approach in different MS types and unresponsiveness of SPMS and PPMS to current immunomodulatory treatment 9 .…”