engleski

The Endocrine-Immune Interactions in PTSD

Objective: Immune response is modulated by positive and negative signalling from neuroendocrine and other bodily tissues. A complex and dynamic molecular network that regulate interactions are influenced by internal and external signals or stressors. Therefore, the stress response can be considered as a study model for neuroendocrine-immune interactions. Distinct profile of hypothalamic-pituitary-adrenocortical (HPA) axis, manifested by low cortisol level and increased number of glucocorticoid receptors (GR), is considered to be characteristic of posttraumatic stress disorder (PTSD). This is congruent with compromised cellular immune response reported in chronic stress. The findings mainly rely on studies performed decades following exposure to trauma. The purpose of this study was to evaluate the effect of combat-associated traumatic experience on hormonal and immune responses in war veterans with PTSD diagnosed by DSM-IV within 8 years after exposure to trauma. Methods: Participants were 39 PTSD sufferers aged 25-50 (mean = 34) years and 37 age matched civilian controls. Serum hormone (cortisol, prolactin, T3, T4) and cytokine (IL-6, TNFalpha) levels were determined by radio- and enzyme immunoassays respectively. The total lymphocyte count and the proportions of total T (CD3), B (CD20) and NK (CD3-CD16, 65+) cells, helper (CD3+CD4+) and cytotoxic (CD3+CD8+) T lymphocytes, CD4 memory (CD4+CD45RO+), and activated B (CD20+CD23+) cell subpopulations were determined by flow cytometry. Polymorphonuclear phagocytic (ingestion, digestion, ADCC) functions, and NK cell activity were measured by 51Cr-release assays. Glucocorticoid receptor expression in lymphocytes and NK cells was determined by flow cytometry after surface phenotyping followed by intracellular staining of GR with anti-GR FITC-labeled MoAb. Results: Serum levels of TNF-alpha and IL-6, cortisol and prolactin were increased in PTSD sufferers as compared to controls. The total lymphocyte count was higher in PTSD patients, as well as proportions of CD3, CD4 and CD8 cells. Although the proportions of NK cells in PTSD did not differ from controls, their cytotoxic activity was enhanced and they had lower GR expression. Glucocorticoid receptor expression was also lower in overall lymphocyte population. No other measured parameters were affected. A canonical correlation revealed multivariate shared relationship between endocrine and both, functional and phenotypic, variables. Conclusions: Several endocrine and immune variables are affected by severe trauma. In early stages of PTSD, i.e. within 8 years following the traumatic event, HPA axis seems to be activated rather than suppressed. This activation could lead to the enhanced negative feedback inhibition described in late PTSD.

War; Trauma; Immune; Endocrine; Flow Cytometry

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