Sex differences in the interleukin-6 response to acute psychological stress

Abstract

Interleukin-6 (IL-6), an immune regulator that helps coordinate the inflammatory response, may mediate inflammatory disease exacerbation associated with stress. Twenty men and twenty women completed a single session, comprising baseline (20 min), mental arithmetic task (8 min), and recovery (60 min). Blood samples, taken at baseline, immediately after the task, and at +30 and +60 min recovery were analysed for plasma IL-6. Overall, IL-6 increased linearly from baseline to +60 min recovery, and a sex difference was found in the IL-6 response, with men peaking earlier than women. These findings confirm a small delayed IL-6 increase after acute laboratory stress, and reveal sex differences in the profile of the IL-6 response.

Introduction

The cytokine interleukin-6 (IL-6) is involved in the regulation of the immune system, activating B and T cells, inducing expression of acute phase proteins, and differentiating monocytes to macrophages (Barton, 1997). There is evidence that IL-6 is elevated in inflammatory disorders, such as rheumatoid arthritis (Nishimoto and Kishimoto, 2004), psoriasis (Ishihara and Hirano, 2002), and eczema (Grangsjo et al., 1996), and that these disorders are exacerbated by stress (Kimyai-Asadi and Usman, 2001, Lechin et al., 1987). It is therefore possible that IL-6 mediates inflammatory disease exacerbation associated with stress.

The evidence concerning the effects of acute laboratory stress on IL-6 is somewhat inconsistent. There have now been five reports that IL-6 increases 45–120 min after performing a 5 min Stroop task followed by 5 min mirror tracing task (Brydon et al., 2004, Kunz-Ebrecht et al., 2003, Owen and Steptoe, 2003, Steptoe et al., 2001, Steptoe et al., 2002). However, IL-6 has also been found to be unchanged by 25 min (Dugue et al., 1993) and 20 min (Lutgendorf et al., 2004) of the Stroop colour word interference task, and by a 45 min battery of stress tasks (mental arithmetic, Stroop, public speaking) in healthy adults (Heesen et al., 2002). The interpretation of these contrasting results is complex. The positive findings have not yet been shown to be robust across different laboratory stressors and populations; all used the same battery of tasks in middle-aged participants, with four of these reports using the same pool of data from the Whitehall II study (Brydon et al., 2004, Kunz-Ebrecht et al., 2003, Owen and Steptoe, 2003, Steptoe et al., 2002). The studies reporting null results are similarly inconclusive; these may be due to low power, shorter sampling intervals (Dugue et al., 1993) or potential confounding associated with the administration of the inflammatory mediator capsaicin (Lutgendorf et al., 2004). Thus, further investigation is clearly warranted.

There is also evidence that there may be sex differences in the IL-6 response to acute stress. Steptoe et al. (2002) reported that women showed greater IL-6 increases 45 min after the acute stress exposure than men. Given the sex dimorphism seen in many inflammatory disorders thought to be exacerbated by stress, the possibility exists that sex differences in the cytokine responses to acute stress may serve as potential mechanism. However, as the findings to date are somewhat tentative, the present study examined the effects of acute psychological stress on IL-6 in young men and women using a mental stress task not previously used in this context. It was hypothesised that IL-6 would increase during the 1 h recovery period, and that larger IL-6 responses would be found in women.