Altered serum stress neuropeptide levels in critically ill individuals and associations with lymphocyte populations

Abstract Objective Potential physiological correlates of stress and the role of stress neuropeptides, other than those of the hypothalamic-pituitary–adrenal axis, in critical illness have not been addressed. We investigated: (a) serum levels of stress neuropeptides (ACTH, substance P (SP), neuropeptide Y (NPY), cortisol, prolactin) in critically ill individuals compared to matched controls, (b) associations with lymphocyte counts, (c) associations among stress neuropeptide levels, and (d) associations with perceived intensity of stress, critical illness severity and survival. Methods Correlational design with repeated measures. Thirty-six critically ill patients were followed up for 14 days compared to 36 healthy matched controls. Stress was assessed by the ICUESS scale. Correlations, cross-sectional comparisons and multiple regression models were pursued. Results For the first time, we report lower SP (Difference of means (DM) = 2928–3286 ng/ml, p p p p r  = 0.411–0.664, p r  = 0.403–0.781, p r  = 0.492–0.690, p r  = 0.39–0.740, p r  = −0.452, p  = 0.01), T-cell ( r  = −0.446, p  = 0.02), T-helper ( r  = −0.428, p  = 0.026) and T-cytotoxic cells ( r  = −0.426, p  = 0.027). ACTH levels associated with NK cell counts ( r  = 0.326–0.441, p p r  = 0.340–0.387, p r  = 0.340, p  = 0.057). Conclusion The significantly lowered NPY and SP levels and the associations with cortisol, ACTH and lymphocytes suggest that the role of these peptides in critical illness merit further investigation. Future studies need to address associations between these neuropeptides and functional immune cell responses and inflammatory markers in critical illness.