Originally published as JCO Early Release 10.1200/JCO.2007.14.1978 on September 8 2008

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Interleukin-6, Cortisol, and Depressive Symptoms in Ovarian Cancer Patients

Susan K. Lutgendorf, Aliza Z. Weinrib, Frank Penedo, Daniel Russell, Koen DeGeest, Erin S. Costanzo, Patrick J. Henderson, Sandra E. Sephton, Nicolas Rohleder, Joseph A. Lucci, III, Steven Cole, Anil K. Sood, David M. Lubaroff

From the Departments of Psychology, Obstetrics and Gynecology, Urology, and Microbiology; Holden Comprehensive Cancer Center, University of Iowa, Iowa City; Department of Veterans Affairs Medical Center, Iowa City; Institute for Social Science Research, Iowa State University, Ames, Iowa; Department of Psychology; Division of Gynecologic Oncology; Sylvester Comprehensive Cancer Center, University of Miami; Department of Psychology, University of Wisconsin, Madison; Department of Psychological and Brain Sciences; James Graham Brown Cancer, University of Louisville, Louisville, KY; Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine; Norman Cousins Center Jonsson Comprehensive Cancer Center; UCLA AIDS Institute; UCLA Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA; Departments of Gynecologic Oncology and Cancer Biology, The University of Texas M.D. Anderson Comprehensive Cancer Center

Corresponding author: Susan Lutgendorf, PhD, E11 Seashore Hall, University of Iowa, Iowa City, IA 52242; e-mail: susan-lutgendorf{at}uiowa.edu

Purpose Inflammatory processes have been implicated in the pathogenesis of both depression and cancer. Links between depressive symptoms, interleukin-6 (IL-6), and cortisol dysregulation have been demonstrated in cancer patients, but vegetative versus affective components of depression have been minimally examined. The objective of the current study was to examine associations between IL-6, diurnal cortisol rhythms, and facets of depression in epithelial ovarian cancer patients.

Patients and Methods Patients awaiting surgery for a pelvic mass suspected for ovarian cancer completed questionnaires, collected salivary samples for 3 days presurgery, and gave a presurgical blood sample. Ascites was obtained during surgery. IL-6 was measured by enzyme-linked immunosorbent assay and cortisol by a chemiluminescence immunoassay. The final sample included 112 invasive ovarian cancer patients (86 advanced stage, 26 early stage) and 25 patients with tumors of low malignant potential (LMP).

Results Advanced-stage ovarian cancer patients demonstrated elevations in vegetative and affective depressive symptoms, plasma IL-6, and the cortisol area under the curve (AUC) compared with patients with LMP tumors (all P < .05). Among invasive ovarian cancer patients, greater vegetative depression was related to elevated IL-6 in plasma (P = .008) and ascites (P = .024), but affective depression was unrelated to IL-6. Elevations in total depression (P = .026) and vegetative depression (P = .005) were also related to higher evening cortisol levels. Plasma IL-6 was related to greater afternoon and evening cortisol and cortisol AUC (all P values < .005).

Conclusion These results demonstrate significant relationships between IL-6, cortisol, and vegetative depression, and may have implications for treatment of depression in ovarian cancer patients.

published online ahead of print at www.jco.org on September 8, 2008.

Supported in part by Grants No. CA88293 and CA104825 (S.K.L.) from the National Cancer Institute.

Presented in part at the Annual Meeting of the Psychoneuroimmunology Research Society, May 30-June 2, 2007, Arcachon, France.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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