This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Wood, L. J. Articles by Druker, B. J. Search for Related Content PubMed PubMed Citation Articles by Wood, L. J. Articles by Druker, B. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ETOPOSIDE Social Bookmarking                   What's this?

The Cancer Chemotherapy Drug Etoposide (VP-16) Induces Proinflammatory Cytokine Production and Sickness Behavior–like Symptoms in a Mouse Model of Cancer Chemotherapy–Related Symptoms

Oregon Health & Science University School of Nursing, 3455 SW US Veterans Hospital Road, Portland, OR 97239; phone: (503) 494 3859; fax: (503) 494 3688; woodl{at}ohsu.edu

Lillian M. Nail, PhD, RN, FAAN

School of Nursing at Oregon Health & Science University, Portland

Nancy A. Perrin, PhD

OHSU School of Nursing, Kaiser Center for Health Research; Portland

Collin R. Elsea, BS

School of Nursing at Oregon Health & Science University, Portland

April Fischer, RN

Brian J. Druker, MD

OHSU Cancer Institute, Center for Hematologic Malignancies at the School of Medicine, Oregon Health & Science University, Portland

Cancer chemotherapy–related symptoms such as fatigue, malaise, loss of interest in social activities, difficulty concentrating, and changes in sleep patterns can lead to treatment delays, dose reductions, or termination and have a profound effect on the physical, psychosocial, and economic aspects of quality of life. Clinicians have long suspected that these symptoms are similar to those associated with "sickness behavior," which is triggered by the production of the inflammatory cytokines IL-1ß, TNF-, and IL-6 by macrophages and other cells of the innate immune system in response to immune challenge. The p38 mitogen-activated protein kinase (p38 MAPK) plays a central role in the production of these cytokines and consequently the induction of sickness behavior. Several cancer chemotherapy drugs have been shown to activate p38 MAPK, but whether these drugs can also induce the production of inflammatory cytokines to cause sickness behavior is unknown. The aim of this study was to determine whether the cancer chemotherapy drug etoposide (VP-16), which is known to activate p38 MAPK, could induce inflammatory cytokine production by murine macrophages and sickness-like behaviors when injected into mice. VP-16 activated p38 MAPK and induced IL-6 production in murine macrophages in a p38 MAPK– dependent manner. VP-16 administration rapidly increased serum levels of IL-6 in healthy mice and induced sickness-like behaviors as evidenced by a decrease in food intake, body weight, hemoglobin level, and voluntary wheel-running activity. These findings support the idea that the induction of IL-1ß, TNF-, and IL-6 by cancer chemotherapy drugs underlies the fatigue and associated symptoms experienced by people undergoing cancer chemotherapy.

Key Words: cancer • chemotherapy • IL-6 • proinflammatory cytokines • sickness behavior • fatigue

Biological Research For Nursing, Vol. 8, No. 2, 157-169 (2006)
DOI: 10.1177/1099800406290932


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. C. Higgins, G. H. Montgomery, G. Raptis, and D. H. Bovbjerg Effect of Pretreatment Distress on Daily Fatigue After Chemotherapy for Breast Cancer J. Oncol. Pract, March 1, 2008; 4(2): 59 - 63. [Abstract] [Full Text] [PDF]