title: 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 < 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nursing B, Faculty of Health and Caring Professions, Technological Educational Institute of Athens, Greece. mmpouzika@yahoo.gr
authors.forename: Meropi D A
authors.initials: MD
authors.lastname: Mpouzika
authors.forename: Elizabeth D E
authors.initials: ED
authors.lastname: Papathanassoglou
authors.forename: Margarita
authors.initials: M
authors.lastname: Giannakopoulou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Bozas
authors.forename: Nicos
authors.initials: N
authors.lastname: Middleton
authors.forename: Sofia
authors.initials: S
authors.lastname: Boti
authors.forename: Elisabeth I
authors.initials: EI
authors.lastname: Patiraki
authors.forename: Andreas
authors.initials: A
authors.lastname: Karabinis
mesh_terms: D018806:APACHE; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016638:Critical Illness; D003430:Cross-Sectional Studies; D005260:Female; D006360:Heat-Shock Proteins / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood; D009478:Neuropeptide Y / Q000097:blood; D009479:Neuropeptides / Q000097:blood*; D011388:Prolactin / Q000097:blood; D012720:Severity of Illness Index; D013373:Substance P / Q000097:blood; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D006360:Heat-Shock Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D013373:Substance P; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006854:Hydrocortisone