Proinflammatory cytokines and sickness behavior: implications for depression and cancer-related symptoms.

PURPOSE/OBJECTIVES To review the relationship between proinflammatory cytokine release and resultant sickness behavior; to explore the implications of sickness behavior related to depression and cancer-related symptoms. DATA SOURCES Published articles and book chapters. DATA SYNTHESIS Proinflammatory cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) are released as part of the immune response resulting in a syndrome called sickness behavior that is an adaptive and motivational reaction to disease. Sickness behavior includes lethargy, depression, anorexia, energy conservation, fever, anhedonia, cognitive impairment, hyperalgesia, and decreased social interaction. Sickness behavior is seen in patients with depression or cancer and has been described as a symptom cluster. Sickness behavior in patients with cancer may be the result of both the disease and the treatment. The related symptoms may have a profound effect on patients' quality of life. Treatment strategies that inhibit the release or activity of proinflammatory cytokines and relieve patients from symptoms of sickness behavior are being evaluated. CONCLUSIONS Further research is needed to pinpoint the exact effects of specific cytokines, identify targets for therapy, and develop viable treatment strategies for preventing or minimizing the detrimental effects of cytokine-induced inflammatory responses. IMPLICATIONS FOR NURSING Sickness behavior resulting from cytokine release may provide a framework to explain many cancer-related symptoms, including depression, cognitive impairment, cachexia, fatigue, and a component of pain perception. Oncology nurses would benefit from awareness and understanding of the relationship between proinflammatory cytokine release and tissue involvement by tumors as well as some cancer-related therapies. Knowledge about the effects of cytokine release on patient behavior and the symptom experience would enhance nurses' ability to assess patients for anticipated side effects and provide appropriate education to patients and their families.

[1]  T. Vial,et al.  Flu-Like Syndrome and Cytokines , 2007 .

[2]  S. Paul,et al.  Symptom clusters and their effect on the functional status of patients with cancer. , 2001, Oncology nursing forum.

[3]  Steven F. Maier,et al.  Immune-to-central nervous system communication and its role in modulating pain and cognition: Implications for cancer and cancer treatment , 2003, Brain, Behavior, and Immunity.

[4]  R. Dantzer.  Cytokine‐Induced Sickness Behavior: Mechanisms and Implications , 2001, Annals of the New York Academy of Sciences.

[5]  S. Vogel,et al.  Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol) in murine and human breast cancer cell lines. , 2001, Cytokine.

[6]  B. Hart.  Biological basis of the behavior of sick animals , 1988, Neuroscience & Biobehavioral Reviews.

[7]  H. Cohen,et al.  Cytokines and Cognition—The Case for A Head‐to‐Toe Inflammatory Paradigm , 2002, Journal of the American Geriatrics Society.

[8]  R. Dantzer.  Cytokine, sickness behavior, and depression. , 2006, Neurologic clinics.

[9]  T. Pollmächer,et al.  Low levels of circulating inflammatory cytokines—Do they affect human brain functions? , 2002, Brain, Behavior, and Immunity.

[10]  R. Dantzer,et al.  Cytokine-induced sickness behavior , 2003, Brain, Behavior, and Immunity.

[11]  R. Dantzer,et al.  Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? , 2003, Cancer.

[12]  J. Kramer,et al.  Potential mechanisms for chemotherapy-induced impairments in cognitive function. , 2005, Oncology nursing forum.

[13]  S. Maier.  Bi-directional immune–brain communication: Implications for understanding stress, pain, and cognition , 2003, Brain, Behavior, and Immunity.

[14]  J. Rossi,et al.  Are inflammatory cytokines the common link between cancer-associated cachexia and depression? , 2005, The journal of supportive oncology.

[15]  C. Nemeroff,et al.  Neurobehavioral Effects of Interferon-α in Cancer Patients: Phenomenology and Paroxetine Responsiveness of Symptom Dimensions , 2002, Neuropsychopharmacology.

[16]  K. Kiura,et al.  Induction of TNF-α, uPA, IL-8 and MCP-1 by doxorubicin in human lung carcinoma cells , 2003, Cancer Chemotherapy and Pharmacology.

[17]  Andrew H. Miller.  Cytokines and sickness behavior: Implications for cancer care and control , 2003, Brain, Behavior, and Immunity.

[18]  M. Wichmann,et al.  Detrimental Immunologic Effects of Preoperative Chemoradiotherapy in Advanced Rectal Cancer , 2003, Diseases of the colon and rectum.

[19]  A. Dunn,et al.  Cytokines as mediators of depression: What can we learn from animal studies? , 2005, Neuroscience & Biobehavioral Reviews.

[20]  A. Saykin,et al.  Breast cancer chemotherapy-related cognitive dysfunction. , 2002, Clinical breast cancer.

[21]  L. Tulman,et al.  Symptom Clusters: Concept Analysis and Clinical Implications for Cancer Nursing , 2005, Cancer nursing.

[22]  S. Maier,et al.  Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. , 1998, Psychological review.

[23]  J. Pruessner,et al.  Individual differences in trait anhedonia: a structural and functional magnetic resonance imaging study in non-clinical subjects , 2007, Molecular Psychiatry.

[24]  A. Harris,et al.  Cytokine Dysregulation, Inflammation and Well-Being , 2005, Neuroimmunomodulation.

[25]  R. Dantzer,et al.  A Cytokine-Based Neuroimmunologic Mechanism of Cancer-Related Symptoms , 2004, Neuroimmunomodulation.

[26]  R. De La Garza.  Endotoxin- or pro-inflammatory cytokine-induced sickness behavior as an animal model of depression: focus on anhedonia. , 2005, Neuroscience and biobehavioral reviews.

[27]  A. Barsevick.  The elusive concept of the symptom cluster. , 2007, Oncology nursing forum.

[28]  S. Larson.  Behavioral and Motivational Effects of Immune-System Activation , 2002, The Journal of general psychology.

[29]  Robert Dantzer,et al.  Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity. , 2004, European journal of pharmacology.

[30]  R. Dantzer,et al.  Expression and regulation of interleukin-1 receptors in the brain. Role in cytokines-induced sickness behavior , 2002, Journal of Neuroimmunology.

[31]  Rodney W. Johnson,et al.  The concept of sickness behavior: a brief chronological account of four key discoveries. , 2002, Veterinary immunology and immunopathology.

[32]  R. Dantzer,et al.  Named Series: Twenty Years of Brain, Behavior, and Immunity Twenty years of research on cytokine-induced sickness behavior , 2007 .

[33]  J. Haddad,et al.  Cytokines and neuro–immune–endocrine interactions: a role for the hypothalamic–pituitary–adrenal revolving axis , 2002, Journal of Neuroimmunology.