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Originally published online as doi:10.1189/jlb.0208133 on August 4, 2008

Published online before print August 4, 2008
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(Journal of Leukocyte Biology. 2008;84:940-948.)
© 2008 by Society for Leukocyte Biology

Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis

Laura Piccio*,1,2, Jennifer L. Stark*,2 and Anne H. Cross*,{dagger}

* Department of Neurology and Neurosurgery and
{dagger} Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA

2 Correspondence: Washington University School of Medicine, Department of Neurology, Campus Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. E-mail: picciol{at}neuro.wustl.edu

ABSTRACT

Calorie restriction (CR) prevents many age-associated diseases and prolongs the lifespan. CR induces multiple metabolic and physiologic modifications, including anti-inflammatory, antioxidant, and neuroprotective effects that may be beneficial in multiple sclerosis (MS). The present studies sought to determine whether CR or increased calorie intake alters the course of experimental autoimmune encephalomyelitis (EAE), the leading animal model for MS. SJL and C57BL/6 mice were subjected to 40% CR beginning at 5 weeks of age. After 5 weeks of CR, EAE was induced by immunizing with proteolipid protein in SJL mice and with myelin oligodendrocyte glycoprotein in C57BL/6 mice. Clinical, histologic, and immunologic features of EAE were compared with mice fed ad libitum and to SJL mice fed a high-fat, high-calorie diet. CR ameliorated clinical EAE in both mouse strains with less severe inflammation, demyelination, and axon injury. No suppression of immune function was observed. A high-calorie diet did not alter the EAE course. CR was associated with increased plasma levels of corticosterone and adiponectin and reduced concentrations of IL-6 and leptin. The CR-induced hormonal, metabolic, and cytokine changes observed in our studies suggest a combined anti-inflammatory and neuroprotective effect. CR with adequate nutrition and careful medical monitoring should be explored as a potential treatment for MS.

Key Words: autoimmunity • inflammation • adipokines • corticosteroids • multiple sclerosis






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