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Title: Altered serum stress neuropeptide levels in critically ill individuals and associations with lymphocyte populations
Authors: Middleton, Nicos 
Papathanassoglou, Elizabeth 
Major Field of Science: Medical and Health Sciences
Field Category: Clinical Medicine
Keywords: Catastrophic illness;Lymphocytes;Neuropeptide Y;Substance P
Issue Date: Feb-2013
Source: Neuropeptides, 2013, vol. 47, no. 1, pp. 25-36
Volume: 47
Issue: 1
Start page: 25
End page: 26
Journal: Neuropeptides 
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<0.001) and NPY (DM =0.77-0.83. ng/ml, p<0.0001) levels in critically ill individuals compared to controls. Cortisol levels were higher (DM = 140-173 ng/ml, p<0.0001) and lymphocyte population counts (p<0.002) were lower in patients throughout the study. NPY levels associated with lymphocyte (r= 0.411-0.664, p<0.04), T-lymphocyte (r= 0.403-0.781, p<0.05), T-helper (r= 0.492-0.690, p<0.03) and T-cytotoxic cell populations (r= 0.39-0.740, p<0.03). On day 1, cortisol levels exhibited associations with lymphocyte (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<0.05). Associations among stress neuropeptides levels were observed throughout (p<0.05). ACTH levels associated with disease severity (r= 0.340-0.387, p<0.005). A trend for an association between ACTH levels and intensity of stress was noted (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.
ISSN: 0143-4179
DOI: 10.1016/j.npep.2012.07.007
Rights: © Elsevier
Type: Article
Affiliation : Technological Educational Institute of Athens 
Cyprus University of Technology 
University of Athens 
Surgical Care Unit, Onassis Cardiac Surgery Center 
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