125. HPA axis habituation to repeated acute psychosocial stress is related to lower sensitization of plasma interleukin-6 responses

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Adaptation to repeated acute stress is understood to be beneficial for health. However, not much is known about the interplay between stress-related (e.g. cortisol) and health relevant biomarkers (e.g. interleukin-6, IL-6) with regard to repeated stress. While HPA axis habituation is regarded as an adaptive response pattern, lower HPA axis responses to repeated stress might theoretically allow disinhibition of inflammatory stress responses, which would be maladaptive. We exposed n = 26 healthy individuals to the Trier Social Stress Test (TSST) on two consecutive days. Salivary cortisol and plasma interleuking-6 (IL-6) were measured repeatedly before and until 2 h after stress on both days. Cortisol and IL-6 significantly increased in response to stress exposure (cortisol p < 0.001; IL-6 p < 0.001). On day 2, average cortisol responses were lower than on day 1, consistent with habituation ( p = 0.011), while IL-6 responses were higher, consistent with sensitization ( p = 0.041). Greater cortisol habituation was a significant predictor of less pronounced IL-6 sensitization ( r = −0.61; p = 0.002). Our findings corroborate the assumption that HPA axis habituation to repeated stress is an adaptive, and not a maladaptive response pattern, because it was related with lower IL-6 responses to repeated stress. Our findings are incompatible with the assumption that high cortisol responses are required for inflammatory control. Intermediate regulatory steps, for example changes in glucocorticoid sensitivity, might explain this finding. Future studies will be needed to understand this intermediate mechanism.