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Abstract: Predicting the individual vulnerability to immune mediated disease is one of the main challenges of modern biomedical research. However, the question of individual behavioral and physiological characteristics that might predict this vulnerability has been subject of research and debate for a long time. This paper will argue that animal models aimed at individual vulnerability should consider the biological function of variation in nature. An increasing number of studies show the ecological significance of variation within a species. Based on behavioral studies in several vertebrate species two coping style can be distinguished. Variation in coping style appears to play a role in the population dynamics and the evolutionary fitness of the species. Coping styles are reflected in a stable differentiation in the behavioral and physiological stress responsiveness over time and across situations. Based on the observations that the individual level of offensive aggressive behavior (i.e., the tendency to defend the home territory) is strongly related to the way animals react to various other environmental challenges, it is argued that the individual’s level of offensiveness is an important indicator and component of a more trait-like behavioral and physiological response pattern (coping style) to environmental demands. The coping style of aggressive animals is principally aimed at a (pro)active prevention or manipulation of a stressor whereas the non-aggressive individuals tend to passively accept or react to it. Proactive coping is associated with high sympathetic reactivity to stressors whereas the more passive or reactive coping style generally has a higher HPA axis reactivity. In view of the immune modulating nature of these major neuroendocrine stress systems, one might expect that coping styles will be reflected in a differential vulnerability to immune mediated disease as well. Indeed, several studies have demonstrated such a relationship, indicating that the functional variation in coping style and related neuroendocrine stress reactivity, as it occurs in nature, might be a good standard for studies aimed at understanding individual vulnerability. This is in agreement with more recent views that also in humans stress reactivity may be the best predictor for the individual vulnerability to immune mediated diseases. This asks for a more fundamental and translational approach of individual disease vulnerability based on a common biological basis of individual differentiation in behavior and physiology in humans and animals. [Copyright &y& Elsevier]

Abstract: Behavioral characteristics closely associated with specific physiological profiles present an important area of research in understanding health disparities. In particular, glucocorticoid overproduction may be an important factor moderating disease progression; natural variance in production of this steroid has been proposed as one mechanism underlying individual differences in health and disease. In the current paper, we examined immune parameters in female rats of two different behavioral types previously shown to have differential glucocorticoid production and life spans. We categorized young female rats according to their behavioral response to novelty (high- or low-locomotion), and compared their glucocorticoid production, adrenal size, thymus size, tumor necrosis factor-α (TNF-α) production, tumor development and life span. As expected, high-locomotion females produced more glucocorticoids and had larger adrenal glands during young adulthood than did low-locomotion females. High-locomotion females had significantly smaller thymuses and reduced TNF-α levels compared to low-locomotion, suggesting altered immune function in young adulthood. Finally, high-locomotion females had shorter life spans than did low-locomotion females, and this was particularly true in females that developed pituitary tumors, but not in those that developed mammary tumors. These results, along with other published findings, suggest that high-locomotion rodent females experience life-long elevations in glucocorticoid responses to novelty, and that these elevated levels may be comparable to chronic stress. This naturally occurring endocrine profile may influence immune responses which in turn could affect disease susceptibility. Variance in immune function across personality types may be partially moderated by natural variance in glucocorticoid production. [Copyright &y& Elsevier]