Plasma cytokine profiles in elderly humans R.J. Forsey a , J.M. Thompson a , J. Ernerudh b, *, T.L. Hurst a , J. Strindhall c , B. Johansson d , B.-O. Nilsson e,f , A. Wikby c a Unilever Research, Colworth House, Sharnbrook MK44 1LQ, UK b Division of Clinical Immunology, Department of Molecular and Clinical Medicine, University of Linko ¨ping, Linko ¨ping, Sweden c Department of Natural Science and Biomedicine, School of Health Sciences, Jo ¨nko ¨ping University, Jo ¨nko ¨ping, Sweden d Department of Psychology, Go ¨teborg University, Go ¨teborg, Sweden e Department of Infectious Diseases, Hospital of Ryhov, Jo ¨nko ¨ping, Sweden f Division of Infection Medicine, Department of Molecular and Clinical Medicine, University of Linko ¨ping, Linko ¨ping, Sweden Received 27 June 2002; received in revised form 7 October 2002; accepted 20 December 2002 Abstract It is known that as we age, immune dysregulation often occurs, leading to failing health, and increased susceptibility to a number of different diseases. In this study we have investigated plasma cytokine profiles in order to identify immune markers of ageing. Plasma samples were obtained from 138 participants of the Swedish longitudinal NONA study (aged 86, 90 and 94 years) and 18 healthy Swedish volunteers (aged between 32 and 59 years). Our results show significantly increased levels of the pro-inflammatory cytokine interleukin-6 (P B/0.0001) and soluble intercellular adhesion molecule-1 (P B/0.0001) in the elderly group. The anti- inflammatory cytokine interleukin-10 did not alter with age whereas active (naturally processed) transforming growth factor-b levels were significantly (P B/0.0001) increased in the elderly group. No difference was observed between males and females. These data suggest that there are measurable changes in cytokine profiles with ageing with increased levels of potentially harmful molecules, which may contribute to immune alterations and declining health in the elderly population. # 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Cytokine; Ageing; sICAM-1; IL-6; IL-10; TGF-b 1. Introduction Cytokines are signal molecules with important effects within, but also outside the immune system. It is suggested that cytokines might be involved in immuno- senescence (Straub et al., 2000). We have chosen to measure the plasma cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), soluble intercellular adhesion molecule-1 (sICAM-1) and transforming growth fac- tor-b (TGF-b), since these are known to be detectable in this medium, have important regulatory roles in inflam- mation, and have been suggested to play a role in the ageing process or are associated with diseases of ageing. IL-6 is a multifunctional, pleiotropic cytokine. IL-6 levels increase after both the menopause and andro- pause, presumably because of a loss of the regulatory influence of secondary sex steroids such as oestrogen. It has been suggested that these age-related increases in IL- 6 account for many of the phenotypic changes seen with advanced age, including decreased lean body mass, osteopenia, low-grade anaemia, decreased serum albu- min and cholesterol, and increased inflammatory pro- teins such as C-Reactive protein and serum amyloid A. Furthermore, this rise in IL-6 has been linked to development of frailty and susceptibility to disease, such as osteoporosis and Alzheimers, in elderly indivi- duals (Ershler and Keller, 2000). sICAM-1 levels have been shown to increase with age (Miles et al., 2001) and are also significantly associated with several established risk factors for cardiovascular diseases (CVD) (Rohde et al., 1998). Due to this correlation several groups have now suggested that * Corresponding author. Blood Center, University Hospital, SE-581 85 Linko ¨ ping, Sweden. Tel.:  /46-13-223269; fax:  /46-13-132257. E-mail address: jan.ernerudh@lio.se (J. Ernerudh). Mechanisms of Ageing and Development 124 (2003) 487  /493 www.elsevier.com/locate/mechagedev 0047-6374/03/$ - see front matter # 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0047-6374(03)00025-3