Endocrine and cytokine responses to standardized physical stress in multiple sclerosis

Heesen, Christoph; Gold, Stefan M.; Hartmann, Sten; Mladek, Mila; Reer, Rüdiger; Braumann, Klaus-Michael; Wiedemann, Klaus; Schulz, Karl‐Heinz

doi:10.1016/s0889-1591(03)00077-1

Cited by 60 publications

(69 citation statements)

References 36 publications

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“…However, endocrine or immunological markers have not been analyzed yet. Recent data from crosssectional findings of our study indicate that MS patients show a slightly hyporeactive cytokine response to acute physical exercise compared to controls while endocrine responses were not altered [12].…”

Section: Introductioncontrasting

confidence: 46%

Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis

Schulz

Gold

Witte

et al. 2004

Journal of the Neurological Sciences

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279

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Section: Introductioncontrasting

confidence: 46%

Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis

Schulz

Gold

Witte

et al. 2004

Journal of the Neurological Sciences

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253

279

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“…Furthermore, the possible mediating biological and especially immune mechanisms have rarely been addressed [26]. Only the Hamburg study investigated immunological and endocrine response markers in a MS exercise study [20,27]. Adrenocorticotropic hormone, cortisol and catecholamines are induced by bicycle exercise in MS patients as in controls without a differential effect [27].…”

Section: Exercise and Immune Function In Msmentioning

confidence: 99%

Physical exercise in multiple sclerosis: supportive care or a putative disease- modifying treatment

Heesen¹,

Romberg²,

Gold³

et al. 2006

Expert Review of Neurotherapeutics

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Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease affecting young adults and leading to considerable disability. For many years, patients have been advised to avoid physical activity. Today, however, an increasing number of studies have shown beneficial effects of exercise training in MS. It has been reported that such programs not only improve fitness parameters but can also enhance quality of life and beneficially affect some suggestive disability measures. Pilot studies even indicate a neuroprotective potential. This review summarizes the findings of the major clinical trials on exercise in MS. Possible biological effect mediators, such as neurotrophic factors or anti-inflammatory cytokines, will be discussed. Exercise management guidelines will be proposed and possible further research strategies are presented.

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“…The foundation for this hypothesis is the well established ability of iron to induce oxidative stress (Halliwell et al, 1992;Robb et al, 1999), the relatively high level of iron staining in oligodendrocytes (Cheepsunthorn et al, 2001;Moos, 2002) and the contribution of oxidative stress to multiple sclerosis (Smith et al, 1999a). Inflammatory cytokines such as interferon-g (IFN-g), tumor necrosis factora (TNF-a) and interleukin-1b (IL-1b) are under investigation as causative or at least major contributors to oligodendrocytic cell death in MS (Merrill and Benveniste, 1996;Leeden and Chakraborty, 1998;Wandinger et al, 2003;Heesen et al, 2003;Tabakman et al, 2004). We believe it is no coincidence that these cytokines also impact iron metabolism (Miller et al, 1991;Pinero et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Cytokine toxicity to oligodendrocyte precursors is mediated by iron

Zhang

Haaf

Todorich

et al. 2005

Glia

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Inflammatory processes play a key role in the pathogenesis of a number of common neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Abnormal iron accumulation is frequently noted in these diseases and compelling evidence exists that iron is involved in inflammatory reactions. Histochemical stains for iron repeatedly demonstrate that oligodendrocytes, under normal conditions, stain more prominently than any other cell type in the brain. Therefore, we examined the hypothesis that cytokine toxicity to oligodendrocytes is iron mediated. Oligodendrocytes in culture were exposed to interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha). Toxicity was observed in a dose-dependent manner for IFN-gamma and TNF-alpha. IL-1beta was not toxic in the concentrations used in this study. The toxic concentration of IFN-gamma, and TNF-alpha was lower if the cells were iron loaded, but iron loading had no effect on the toxicity of IL-1beta. These data provide insight into the controversy regarding the toxicity of cytokines to oligodendrocytes by revealing that iron status of these cells will significantly impact the outcome of cytokine treatment. The exposure of oligodendrocytes to cytokines plus iron decreased mitochondrial membrane potential but activation of caspase 3 is limited. The antioxidant, TPPB, which targets mitochondria, protected the oligodendrocytes from the iron-mediated cytotoxicity, providing further support that mitochondrial dysfunction may underlie the iron-mediated cytokine toxicity. Therapeutic strategies involving anti-inflammatory agents have met with limited success in the treatment of demyelinating disorders. A better understanding of these agents and the contribution of cellular iron status to cytokine toxicity may help develop a more consistent intervention strategy.

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Endocrine and cytokine responses to standardized physical stress in multiple sclerosis

Cited by 60 publications

References 36 publications

Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis

Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis

Physical exercise in multiple sclerosis: supportive care or a putative disease- modifying treatment

Cytokine toxicity to oligodendrocyte precursors is mediated by iron

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