Stress and depression-induced immune dysfunction: implications for the development and progression of cancer.
The persistent activation of the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary axes in chronic stress response and in depression impairs the immune response and contributes to the development and progression of some types of cancer. This overview presents results from experimental animal models, human studies, and clinical evidence that various cellular and molecular immunological parameters are compromised in chronic stress and depression. At the cellular level, stressed and depressed patients had overall leukocytosis, high concentrations of circulating neutrophils, reduced mitogen-stimulated lymphocyte proliferation and neutrophil phagocytosis. At the molecular level, high levels of serum basal cortisol, acute phase proteins, specific antibodies against herpes simplex virus type 1 and Epstein Barr virus, plasma concentration of interleukins IL-1, IL-6, and TNF-alpha, and a shift in the balance of Th1 and Th2 immune response were observed. Both stress and depression were associated with the decreased cytotoxic T-cell and natural killer cell activities affecting the processes of the immune surveillance of tumours, and the events that modulate the development and the accumulation of somatic mutations and genomic instability. DNA damage, growth and angiogenic factors, proteases, matrix metalloproteinases, and reactive oxygen species were also related to the chronic stress response and depression. Behavioural strategies, psychological, and psychopharmacotherapeutic interventions that enhance effective coping and reduce affective distress showed beneficial effects in cancer patients. A better understanding of the bidirectional communication between the neuroendocrine and immune systems could contribute to novel clinical and treatment strategies in oncology.
Reiche
Edna Maria Vissoci
EM
Department of Pathology, Clinical Analysis and Toxicology, State University of Londrina, Londrina, Paraná, Brazil. reiche@sercomtel.com.br
Morimoto
Helena Kaminami
HK
Nunes
Sandra Morimoto Vargas
SM
D000914:Antibodies, Viral / Q000097:blood; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D003863:Depression / Q000150:complications / Q000276:immunology; D003866:Depressive Disorder / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007111:Immunity, Cellular / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D009369:Neoplasms / Q000276:immunology* / Q000523:psychology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011598:Psychoneuroimmunology; D018139:Simplexvirus / Q000276:immunology; D013315:Stress, Psychological / Q000150:complications* / Q000276:immunology / Q000523:psychology
D000914:Antibodies, Viral; D018836:Inflammation Mediators