Original article
Impairment of several immune functions in anxious women

https://doi.org/10.1016/j.jpsychores.2006.07.030Get rights and content

Abstract

Objective

Controversial results concerning immune function changes taking place in anxious subjects have been obtained. The aim of the present work was to study immune function in a group of anxious women.

Methods

Thirty-three anxious and 33 nonanxious age-matched women were included. Anxiety levels were determined by the Beck Anxiety Inventory. Peripheral blood samples were collected, and several leukocyte functions, as well as cytokine release, were studied. Plasma cortisol levels and total antioxidant capacity were also evaluated.

Results

The results showed diminished chemotaxis, phagocytosis, lymphoproliferation in response to phytohemagglutinin mitogen, natural killer activity, and interleukin-2 release, and augmented superoxide anion levels and tumor necrosis factor-α release in anxious women. Plasma cortisol was increased, while total antioxidant capacity was lowered in those subjects.

Conclusions

The findings suggest impaired immune function and cytokine release in anxious women. This might be related to increased cortisol secretion, which would lead to oxidative stress reflected in lowered plasma total antioxidant capacity.

Introduction

The hypothalamic–pituitary–adrenocortical (HPA) axis is a neuroendocrine system of great interest for the study of the relationship between stress and health. Immune cells exhibit receptors for many neuroendocrine products, such as those from the HPA axis [1]. Besides, the principal glucocorticoid modulating anxiety is cortisol [2], which causes changes in immune cellular functions [3]. Accordingly, many authors suggest that anxiety may negatively affect lymphocyte proliferative response to phytohemagglutinin (PHA) and to concanavalin A, and natural killer (NK) cell activity, although it may also be associated with a lack of significant differences or even increased functions. This last response is considered a transient phenomenon occurring prior to immune down-regulation, indicating the body's defense against stressors and thus dealing with state (discrete response to a specific threatening situation) anxiety as opposed to trait (general tendency to experience anxiety symptoms when faced with nondangerous situations) anxiety [4], [5], [6], [7]. Nevertheless, research dealing with the relation of anxiety to immunity is scarce [5].

Cytokines are known to orchestrate the complex network of cellular interactions that regulate immune response. Some studies have shown a decreased PHA-induced interleukin-2 (IL-2) production [6] in anxious patients, while several found a positive correlation [4]. Proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), appear to be increased [8] in those patients.

Some authors have hypothesized on the important role that phagocytic cells play in immune changes experienced by subjects with emotional disturbances [9]. Reactive oxygen species (ROS) produced by phagocytes are important for host defense and as intracellular messengers needed for cellular functioning. However, excessive production and/or release of ROS is deleterious for immune cells, leading to oxidative stress [10]. Cell homeostasis and, consequently, cell functions would be compromised by an imbalance between oxidants and antioxidants [11]. Therefore, adequate amounts of neutralizing antioxidants are required to prevent cellular damage, especially in immune cells [10].

In view of controversial results observed with regard to immune function changes exhibited by anxious subjects, the present work deals with the study of some key lymphocyte and neutrophil functions, and of cytokine release. These functions have previously been evaluated by our research group in anxious mice, showing alterations that have correlated with the life span of the animals [12], [13], [14]. Moreover, several of the above functions have been shown to be good health markers [12], [13], [14], [15]. In addition, in view of the above, plasma cortisol and total antioxidant capacity were also studied.

Section snippets

Subjects

The study was performed on 33 women aged 43.29±2.09 years who showed high levels of anxiety (53.8±7.1; P<.001 with respect to controls), as determined by the Beck Anxiety Inventory (BAI) [16], [17], [18]. The control group was composed of 33 nonanxious women (4.32±3.43) of the same age (43.29±2.09 years) to avoid age-related and gender-related differences.

Participants were individuals who responded to e-mail, press advertisements, and posters. All subjects were Spanish and were recruited from

Neutrophil functions

There were no differences in neutrophil adherence capacity between anxious and nonanxious women (AI=50±4 and 50±2, respectively). In regard to chemotaxis function (Fig. 1A), anxious subjects showed an index (CI=307±24) significantly (P<.001) lower than that of the control group (CI=528±15). The PI (Fig. 1B) was decreased in anxious women (PI=174±27; P<.01), as compared to that in their nonanxious counterparts (PI=348±45). In addition, the percentage of phagocytosing cells (Fig. 1C) was lower (P

Discussion

Maintaining a good functioning of immune cells has been shown to be a health and longevity marker, which has been demonstrated specifically as regards chemotaxis, phagocytosis, superoxide anion levels, lymphoproliferation, IL-2 release, NK activity, and TNF-α release [12], [13], [14]. However, since there are controversial data concerning immune function changes exhibited by anxious subjects, more studies are needed to understand them better. Thus, the aim of the present work was to study

Acknowledgments

This work was supported by a grant from the Spanish Ministry of Education and Science (BFU2005-06777).

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