Supportive Care in Cancer

, Volume 21, Issue 8, pp 2097–2106 | Cite as

Associations of interleukin-6 with vegetative but not affective depressive symptoms in terminally ill cancer patients

  • Masatoshi Inagaki
  • Tatsuo Akechi
  • Toru Okuyama
  • Yuriko Sugawara
  • Hiroya Kinoshita
  • Yasuo Shima
  • Kimio Terao
  • Shuichi Mitsunaga
  • Atsushi Ochiai
  • Yosuke UchitomiEmail author
Original Article



Previous studies have reported associations of depressive symptoms with pro-inflammatory cytokines, especially with interleukin-6 (IL-6) in noncancer subjects and cancer patients. Meanwhile, symptoms such as tiredness and appetite loss may be vegetative symptoms of depression when associated with other diagnostic criteria of depression. Such vegetative-type symptoms worsen during the last 6 months of life in cancer patients and may not be associated with affective depressive symptoms such as sadness and nervousness. This study explored associations between depressive symptoms and plasma IL-6 in terminally ill cancer patients whose survival period was confirmed to be less than 6 months by follow-up, with attention to differences in vegetative and affective depressive symptoms.


Data from 112 consecutively recruited terminally ill cancer patients who registered at a palliative care unit without any active anticancer treatment were used. Plasma IL-6 levels were measured using an electrochemiluminescence assay. Depressive symptoms included in the DSM-IV and Cavanaugh criteria were assessed by structured interviews and were categorized into affective symptoms and vegetative symptoms. Affective symptoms were also measured with the depression subscale of the Hospital Anxiety and Depression Scale, which does not include vegetative symptoms.


Vegetative symptoms, such as appetite loss, insomnia, and fatigue, were significantly associated with IL-6 levels. However, neither of the affective symptoms nor their severity was associated with IL-6 levels.


IL-6 was associated with vegetative depressive symptoms in terminally ill cancer patients but not with affective depressive symptoms, suggesting possible differences in the pathophysiological mechanisms between these sets of symptoms.


Depression Fatigue Terminal illness Cytokine Sickness behavior Cancer 



This study was supported in part by a third-term Comprehensive Control Research for Cancer grant from the Japanese Ministry of Health, Labour, and Welfare; a grant from the Japan Society for the Promotion of Science; and a grant from the Japanese Ministry of Education, Culture, Science, and Technology. Cytokine measurements were funded by Chugai Pharmaceutical Co., Ltd., Tokyo, Japan. These funding agencies had no role in the study design, data collection, analysis, or interpretation of the results. The authors specially thank Dr. Mitsuhiko Yamada for his valuable suggestions. The authors thank Ms. Nobue Taguchi and Yuko Kojima for their research assistance. We also express special thanks to all participants in this study.

Conflict of interest

Kimio Terao is an employee of Chugai Pharmaceutical Co., Ltd., Tokyo, Japan. Other authors have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Masatoshi Inagaki
    • 1
    • 2
  • Tatsuo Akechi
    • 3
  • Toru Okuyama
    • 3
  • Yuriko Sugawara
    • 4
  • Hiroya Kinoshita
    • 5
  • Yasuo Shima
    • 6
  • Kimio Terao
    • 7
  • Shuichi Mitsunaga
    • 8
    • 9
  • Atsushi Ochiai
    • 9
  • Yosuke Uchitomi
    • 10
    • 11
    Email author
  1. 1.Center for Suicide PreventionNational Institute of Mental Health, National Center of Neurology and PsychiatryTokyoJapan
  2. 2.Department of NeuropsychopharmacologyNational Institute of Mental Health, National Center of Neurology and PsychiatryTokyoJapan
  3. 3.Department of Psychiatry and Cognitive-Behavioral MedicineNagoya City University Graduate School of Medical SciencesNagoyaJapan
  4. 4.NISSAN Motor Health Insurance SocietyAtsugi, KanagawaJapan
  5. 5.Department of Palliative MedicineNational Cancer Center Hospital EastChibaJapan
  6. 6.Department of Palliative MedicineTsukuba Medical Center HospitalIbarakiJapan
  7. 7.Clinical Pharmacology DepartmentChugai Pharmaceutical Co., LtdTokyoJapan
  8. 8.Division of Hepatobiliary and Pancreatic OncologyNational Cancer Center Hospital EastKashiwaJapan
  9. 9.Pathology Division, Research Center for Innovative OncologyNational Cancer Center Hospital EastKashiwaJapan
  10. 10.Psycho-Oncology Division, Research Center for Innovative OncologyNational Cancer Center Hospital EastKashiwaJapan
  11. 11.Department of NeuropsychiatryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan

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