Pilot Investigation of the Association Between Serum Stress Neuropeptide Levels and Lymphocyte Expression of Fas and Fas Ligand in Critical Illness

Introduction: In critical illness, apoptotic loss of immunocytes is associated with immunosuppression. Aim: To explore expression of Fas/Fas ligand (FasL) on B and T cells from critically ill patients without sepsis compared to matched controls and associations with disease severity and neuropeptide Y (NPY), cortisol, adrenocorticotropic hormone (ACTH), and prolactin (PRL) levels. Methods: Repeated-measures correlational design with 36 critically ill patients (14-day follow-up) and 36 controls. Disease severity was assessed using the Multiple Organ Dysfunction Score (MODS) and Multi Organ Failure scale. Fas/FasL values were standardized for viable cell counts. An enzyme-linked immunosorbent assay (NPY) and electrochemiluminescence immunoassay (cortisol, ACTH, and PRL) were employed. Results: Fas and FasL expression on T-helper (p < .0001-.03) and T-cytotoxic cells (p < .0001-.002) and Fas expression on B cells (p < .0001-.03) were higher in patients. MODS severity was associated with FasL expression on cytotoxic T cells (r = .752-.902, p = .023-.037). There was an inverse association between Day 1 NPY levels and Fas expression on T-helper cells (r = -.447, p = .019). On the day of maximum severity, we report for the first time an inverse association between NPY levels and FasL expression on helper (r = -.733, p = .016) and cytotoxic (r = -.862, p = .003) T cells. Cortisol levels were positively associated with counts of FasL-positive helper (r = .828) and cytotoxic (r = .544, p < .05) T cells. Conclusion: Results suggest a potential role for stress neuropeptides in lymphocyte survival and activation in critical illness.