Endocrine and cytokine responses to standardized physical stress in multiple sclerosis Christoph Heesen, a, * Stefan M. Gold, a,b Sten Hartmann, b,a Mila Mladek, a R€ udiger Reer, c Klaus-Michael Braumann, c Klaus Wiedemann, d and Karl-Heinz Schulz b a Department of Neurology, University Hospital Eppendorf, Martinistrasse 53, D-20246 Hamburg, Germany b Institute of Medical Psychology, University Hospital Eppendorf, Hamburg, Germany c Institute for Sports and Exercise Medicine, University of Hamburg, Hamburg, Germany d Department of Psychiatry, University Hospital Eppendorf, Hamburg, Germany Received 28 January 2003; received in revised form 28 February 2003; accepted 24 March 2003 Abstract Since the earliest descriptions psychological and physical stress has been considered a controversial but potentially important factor in the onset and course of multiple sclerosis (MS). During recent years it has become clear that MS patients benefit from physical exercise as performed in aerobic training. As acute exercise has profound effects on immune and endocrine parameters we studied endocrine and immune response to standardized physical stress in MS within a study of aerobic training. Fifteen MS patients completed an eight-week aerobic training program, 13 patients were part of a wait-control group. Twenty healthy controls were recruited as well. A step-by-step bicycle ergometry was performed to determine individual exertion levels. For the endurance test patients exercised at 60% VO 2 max for 30 min. Blood samples were drawn before, directly after and 30 min after completion of the exercise. Heart rate and lactate increased in all groups (p <:0001). We furthermore saw significant increases in endocrine parameters (epinephrine, norepinephrine, ACTH, and b-endorphin; all p <:0001) in healthy individuals and in MS patients but without a differential effect. Whole-blood stimulated production of IFN-gamma (IFNc) was induced similarly in all groups (p <:01). TNF-alpha (TNFa) and IL-10 were less inducible in MS patients (trend). From these data we could not demonstrate a proinflammatory immune deviation in response to physical stress in MS. The observed trend of hyp- oresponsive TNFa and IL-10 responses in MS warrants further investigation. Ó 2003 Elsevier Science (USA). All rights reserved. Keywords: Multiple sclerosis; Physical exercise; IFN-gamma; TNF-alpha; Interleukin-10; Catecholamines; HPA axis; b-endorphin 1. Introduction Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by different pat- terns of inflammation, demyelination and axonal loss. Recent findings suggest that the pathogenesis of MS is much more heterogeneous than previously assumed (Lucchinetti et al., 2000). Nevertheless, an increasing body of evidence from studies investigating immune, neural, and endocrine pathways indicates that MS is a predominantly immunodysregulatory disease. Based on the studies of experimental autoimmune encephalomy- elitis (EAE), a dysregulation of the balance between proinflammatory T helper 1 (TH-1 type) and anti-in- flammatory (TH-2 type) cytokines with a shift to a TH-1 profile has been postulated in MS (Van Boxel-Dezaire et al., 1999). Brain, Behavior, and Immunity 17 (2003) 473–481 www.elsevier.com/locate/ybrbi BRAIN, BEHAVIOR, and IMMUNITY * Corresponding author. Fax: +49-40-42803-6973. E-mail address: heesen@uke.uni-hamburg.de (C. Heesen). 0889-1591/$ - see front matter Ó 2003 Elsevier Science (USA). All rights reserved. doi:10.1016/S0889-1591(03)00077-1