Stress, genetics, and immunity

Biomedical researchers have for long tried to avoid individual variation as much as possible by using inbred strains of animals or cloned cells under standardized conditions. In the field of psychoneuroimmunology, the contribution of individual variation to functional outcome has been recognized and studied in a more systematic way as an aspect that should not be discarded, but should be investigated to understand how the phenotype of an individual is shaped. This special issue of Brain, Behavior, and Immunity contains original research articles focusing on individual differences in stress responsivity and immunity. It is now generally accepted that exposure to acute or chronic stress will evoke changes in behavior, the neuroendocrine system, and in the activity of the immune system and may thereby contribute to susceptibility to infection and to immune-mediated diseases including autoimmunity and asthma. Studies in both inbred and outbred strains of animals as well as in humans on the role of neuro-immune interactions in disease have revealed the contribution of individual variability in the stress response and in the immune response to outcome (Cohen and Hamrick, 2003). For example, we have described that within an inbred population of Lewis rats, animals can be identified that have a high or low locomotor response in an open field. More importantly, our data demonstrated that the activity of Lewis rats in the open field can predict outcome in an animal model of rheumatoid arthritis and in a model of tumor cell metastasis and tumor angiogenesis (Sajti et al., 2004a,b). Although the actual inflammatory activity as determined by paw swelling, redness and immobility was similar in high and low active animals, there was a marked difference in joint destruction between the two groups (Sajti et al., 2004a). In addition, we showed that inbred Lewis rats that display high activity in the open field, develop more metastases after intravenous administration of tumor cells and have a stronger angiogenic response to the tumor (Sajti et al., 2004b). The latter data underline that outcome is not only determined by the genotype. Probably environmental conditions during critical "windows" throughout development, program homeostatic systems that shape our phenotype.