Immune-endocrine host response to endotoxin in major depression.
OBJECTIVE
An impaired hypothalamic-pituitary-adrenocortical (HPA) function is a well-established finding in major depression (MD), but it is still unclear how this dysfunction affects immune responses in this disorder.


METHODS
To further examine the relationship between immune and endocrine responses in MD, 0.4ng/kg body weight endotoxin [LPS] or 100mug hCRH were sequentially applied to 12 patients with MD and to 12 age- and gender-matched healthy controls after pre-treatment with 1.5mg dexamethasone (DEX). Immune (TNF-alpha, IL-6, rectal temperature) and endocrine (ACTH, cortisol) parameters were examined as area under the curve (AUC) levels.


RESULTS
After pre-treatment with DEX, LPS evoked an immune response in all participants of the study with most immune parameters significantly related to the endotoxin challenge. However, only a marked immune response resulted in an additional endocrine reaction. Subsequently, the quantitative extent of the endocrine reaction was related to the extent of the immune response after DEX/LPS challenge. Pre-LPS AUC levels of cortisol, ACTH and post-LPS levels of IL-6 as well as the post-CRH AUC levels of cortisol and ACTH were related to the depressive symptomatology as measured by the Beck depression inventory (BDI). In depressive patients who showed increased cortisol plasma levels before LPS, the later increase in IL-6 was reduced.


CONCLUSIONS
The challenge with DEX/LPS did not reveal major impairments of evoked immune functions in MD. Only the endocrine parameters and the IL-6 response were related to the depressive symptomatology, suggesting a limited interaction between immune and endocrine dysfunctions in MD.
Vedder
Helmut
H
Max Planck Institute of Psychiatry, Munich, Germany. vedder@med.uni-marburg.de
Schreiber
Wolfgang
W
Schuld
Andreas
A
Kainz
Martin
M
Lauer
Christoph Johannes
CJ
Krieg
Jürgen-Christian
JC
Holsboer
Florian
F
Pollmächer
Thomas
T
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001831:Body Temperature / Q000276:immunology; D016022:Case-Control Studies; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D003865:Major Depressive Disorder / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D003907:Dexamethasone / Q000008:administration & dosage; D004703:Endocrine System / Q000187:drug effects / Q000503:physiopathology*; D004731:Endotoxins / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007109:Immunity / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone