Stress and immune regulation

Abstract

The paper by Olgart Hoglund and colleagues published in this issue examines the association between examination stress, systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic undergraduate students [1]. It brings a careful analysis of various components of immune regulation to the study of psychological influences of asthma, which one of us previously described as having a long and chequered history [2]. Examination stress has been used to study various aspects of immune activation [3, 4] but this study represents the first description of an increased number of regulatory T cells in peripheral blood, observed in both atopic and non-atopic students, as well as a skewed Th1/ Th2 ratio and reduced natural killer (NK) cell numbers that were unique to atopic students. Interestingly, Olgart Hoglund and colleagues noted that the group of students characterized by high perceived stress levels at baseline had higher numbers of CD4CD45ROCD25 than the group with low perceived stress at the baseline (non-exam) period, suggesting that numbers of regulatory T cells increase with increased stress levels. NK cells were decreased in atopics in response to stress, but the techniques used to quantitate these, while specific for NK cells as stated by the authors, do not address the numbers of NKT cells. A future study might offer some further interesting insights into the respective roles of these latter cells which may contribute to either the pathogenic or protective processes underlying asthma, with some studies showing that NKT cells are essential for development of allergic asthma but others reporting that treatment with specific NKT ligands inhibits airway hyper-reactivity, eosinophilia and IgE production [5]. Furthermore, the relations between baseline stress levels, changes in stress from the no-exam to the exam period and immune or pulmonary function parameters were complex. For example, there were no differences in any investigated parameters when the group of students with a large increase in perceived stress or cortisol levels from baseline to exam period was compared with a group of students with minimal changes in perceived stress or cortisol. This calls into question whether the visual analogue scale used to assess perceived stress is sensitive to change and whether the group was adequately powered to support analyses by subgroups. This is not a trivial issue when we consider that only 41 students had to be divided into several subgroups. A lack in description of the statistics used enhanced the challenge of sorting out main effects from interactions in this report. Although a modest number of studies such as this one by Olgart Hoglund have examined the impact that the activity of the stress system may have on immune activation and asthma symptoms, fewer studies have considered whether immune activation and the experience of having asthma, particularly during childhood, influences the long-term responsiveness of the HPA axis. Furthermore, few have considered what the impact of this long-term dysregulation of the HPA axis could mean to the course and severity of asthma and other immune-related diseases. Kean et al. [6] recently reported rates of posttraumatic stress, presumably analogous to post-traumatic stress disorder (PTSD, associated with chronic alterations in HPA axis function), in adolescents with life-threatening asthma. Twenty percent of adolescents with life-threatening asthma had PTS, compared with 8% of healthy controls. Provocatively, almost 1/3 (29%) of the parents of adolescents with life threatening asthma had PTS compared with only 2% of the parents of healthy controls. Parental rates of PTS were elevated (14%) for parents of children with non-life-threatening asthma as well. If the reported rates of PTS are roughly equivalent to a PTSD diagnosis in these subjects, then the rates of PTSD are comparable to those observed in populations exposed to the most challenging and chronically stressful conditions such as war. Kean et al. [6] also found a relation between Correspondence: Dr John Bienenstock, Department of Pathology and Molecular Medicine Room 3N26, McMaster University Health Sciences Centre 1200 Main Street, West Hamilton, ON Canada L8N 3Z5. E-mail: Bienens@mcmaster.ca Clinical and Experimental Allergy, 36, 969–971