Psychological stress and the inflammatory response system.

In this issue of Clinical Science, Steptoe et al. [1] report that acute psychological stress in humans (computerized colour-word interference task and mirror tracing) significantly increases the serum concentrations of interleukin-6 (IL-6) and the IL-1 receptor antagonist (IL-1Ra). IL-6 is a pleiotropic cytokine which is involved in T-cell activation, B-cell differentiation and the initiation of the acute-phase response [2]. The IL-1Ra is produced by and released from activated cells of the monocyte\ macrophage lineage. It is a pure IL-1 receptor antagonist which may inhibit some of the pro-inflammatory effects of IL-1 [2]. Thus the results of Steptoe et al. [1] suggest that psychological stress elicits an activation of the inflammatory response system (IRS). These important findings of Steptoe et al. [1] extend those of previous studies performed in experimental animals and humans. Indeed, in experimental animals, plasma IL-6 concentrations and the expression of IL-6 mRNA in the midbrain are significantly elevated by various psychological stressors, such as exposure to electric foot shocks, physical restraint, immobilization stress, open field stress and other aversive stimuli (reviewed in [3]). Recently, it was shown : (i) that peripheral corticotropin-releasing hormone mediates the plasma IL-6 elevations in response to immobilization stress [4] ; and (ii) that the liver, and not the intestinal microflora, is one of the major sources responsible for increased plasma IL-6 during restraint stress [5]. Our laboratory was the first to report that in healthy volunteers academic examination stress significantly elevated the stimulated production of IL-6 by whole blood [6]. These findings were replicated by Paik et al. [7]. The speaking task, another acute psychological stressor, significantly increases the lipopolysaccharide-induced production of IL-6 [8]. In older women, chronic stressors are associated with significant elevations in plasma IL-6 [9]. In patients with rheumatoid arthritis, plasma IL-6 is significantly elevated only when there is mental stress [10]. There are only a few papers which have examined the effects of psychological stress on the IL-1Ra. Thus in various rat brain regions immobilization stress significantly increases IL-1Ra and IL-1 levels [11]. Song et al. [12] reported that academic examination stress increases plasma IL-1Ra concentrations only in students who experience high levels of subjective distress. Also, the production of IL-1Ra by stimulated whole blood is significantly increased by academic examination stress [6]. It should be emphasized that a large number of other studies report that psychological stress may activate the IRS. In the rodent, various stressors, such …