An immunological model connecting the pathogenesis of stress, depression and carcinoma.
Recently there has been considerable conjecture in the literature concerning a possible relationship between stress, depression and bereavement, and carcinoma. We shall propose a causal model in which the relationship between stress, depression and carcinoma is clarified. This relationship is grounded on dysregulation of the inflammatory cytokines in stress and depression. Stress is associated with increased expression of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), and reduced expression of IL-2, interferon-gamma (IFN-gamma), major histocompatability complex (MHC) class II molecules and natural killer cell activity (NKA). Depression is associated with elevated IFN-gamma and IL-1 beta, downregulated IL-2, and reduced NKA. Most organ-related carcinomas are associated with elevated TNF-alpha, which inhibits the activity of protein tyrosine phosphatase (PTPase), the enzyme that initiates activation of the MHC class I pathway. Sustained elevation of TNF-alpha inhibits the activity of PTPase which results in diminished expression of the MHC class I antigen on the cell surface and thus, malignant cells escape immune surveillance. Therefore, stress and depression can foster tumor progression by means of inhibiting the expression of MHC class I and II molecules and through the reduction of NKA.
Holden
R J
RJ
Medical Research Unit, University of Wollongong, NSW, Australia.
Pakula
I S
IS
Mooney
P A
PA
D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003863:Depression / Q000150:complications / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000209:etiology / Q000276:immunology*; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D001615:beta-Endorphin / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D001615:beta-Endorphin; D007371:Interferon-gamma