Brain, Behavior, and Immunity 21 (2007) 209–217 www.elsevier.com/locate/ybrbi 0889-1591/$ - see front matter  2006 Elsevier Inc. All rights reserved. doi:10.1016/j.bbi.2006.04.158 Eccentric exercise as an adjuvant to inXuenza vaccination in humans Kate M. Edwards a,¤ , Victoria E. Burns a , Louise M. Allen a , Jamie S. McPhee a , Jos A. Bosch a , Douglas Carroll a , Mark Drayson b , Christopher Ring a a School of Sport and Exercise Sciences, University of Birmingham, UK b Department of Immunology, School of Medicine, University of Birmingham, UK Received 27 February 2006; received in revised form 27 April 2006; accepted 27 April 2006 Available online 7 July 2006 Abstract The immune response to vaccination in animals can be enhanced by exposure to acute stress at the time of vaccination. The eYcacy of this adjuvant strategy for vaccination in humans requires investigation. The current study employed a randomised controlled trial design to examine the eVects of eccentric exercise prior to inXuenza vaccination on the antibody and cell-mediated responses. Sixty young healthy adults (29 men, 31 women) performed eccentric contractions of the deltoid and biceps brachii muscles of the non-dominant arm (exercise group) or rested quietly (control group), and were vaccinated 6 h later in the non-dominant arm. Change in arm circumference and pain were measured to assess the physiological response to exercise. Antibody titres were measured pre-vaccination and at 6- and 20- week follow-ups. Interferon- in response to in vitro stimulation by the whole vaccine, an index of the cell-mediated response, was mea- sured 8 weeks post-vaccination. Interferon- responses were enhanced by exercise in men, whereas antibody titres were enhanced by eccentric exercise in women but not in men. Men showed greater increase in arm circumference after eccentric exercise than women but there was no diVerence in reported pain. The interferon- response was positively associated with the percentage increase in arm circum- ference among the exercise group. Eccentric exercise exerted diVerential eVects on the response to vaccination in men and women, with enhancement of the antibody response in women, but enhancement of the cell-mediated response in men. Eccentric exercise of the muscle at the site of vaccine administration should be explored further as a possible behavioural adjuvant to vaccination.  2006 Elsevier Inc. All rights reserved. Keywords: Eccentric exercise; Antibody; Cell-mediated; InXuenza vaccination 1. Introduction InXuenza is a major cause of morbidity and mortality, responsible for between 200 and 30,000 deaths annually in the UK (Crofts et al., 2003). The inXuenza vaccination pro- vides up to 50% protection against infection (Govaert et al., 1994), reducing hospitalisation and deaths (Nichol et al., 1994). However, the sizeable proportion of individuals with inadequate antibody responses to vaccination has pro- pelled a search for adjuvants to increase vaccine eYcacy. In addition to traditional pharmacological adjuvants, behav- ioural and endogenous adjuvants have recently been advo- cated (Gallucci et al., 1999; Viswanathan et al., 2005). For example, studies in rodents have provided accumulating evidence that acute stress prior to antigen exposure can enhance cellular (e.g., delayed-type hypersensitivity) (Ble- cha et al., 1982; Dhabhar and McEwen, 1996, 1997, 1999; Saint-Mezard et al., 2003) and humoral (i.e., antibody) responses (Millan et al., 1996; Persoons et al., 1995; Silber- man et al., 2003; Wood et al., 1993). In the literature acute stress is operationalised as an acute psychological stress event or a single bout of exercise. While there is evidence that chronic exposure to either psy- chological stress or exercise training protocols can inXuence antibody response to vaccination (Burns et al., 2003; Kohut et al., 2004; Smith et al., 2004), there has been considerably less focus on the eYcacy of acute exposures immediately prior to vaccination. However, there is now preliminary * Corresponding author. Fax: +44 121 414 4121. E-mail address: K.Edwards.1@bham.ac.uk (K.M. Edwards).