Originally published as JCO Early Release 10.1200/JCO.2008.18.7435 on May 11 2009

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Biologic Cost of Caring for a Cancer Patient: Dysregulation of Pro- and Anti-Inflammatory Signaling Pathways

From the Department of Psychology, Brandeis University, Waltham, MA; and Department of Psychology, University of British Columbia; and British Columbia Cancer Agency, Vancouver Centre, Vancouver, British Columbia, Canada.

Corresponding author: Nicolas Rohleder, PhD, Brandeis University, Department of Psychology, MS 062, PO Box 549110, Waltham, MA 02454; rohleder{at}brandeis.edu.

Purpose Caring for a family member with cancer is a psychologically demanding experience. However, it remains unclear whether the distress that caregiving provokes also takes a physiologic toll on the body. This study observed familial caregivers of patients with brain cancer for a year after diagnosis and tracked changes in neurohormonal and inflammatory processes.

Patients and Methods Eighteen caregivers (age 50.4 ± 3.5 years) and 19 controls (age 50.2 ± 2.6 years) were assessed four times during a year (before and after radiotherapy, as well as 6 weeks and 4 months thereafter). Salivary biomarkers of hypothalamus-pituitary-adrenal axis and sympathetic nervous system (SNS) activity were collected, and blood was drawn for assessment of the systemic inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6). Blood was also used to monitor in vitro IL-6 production by endotoxin-stimulated leukocytes and expression of mRNA for pro- and anti-inflammatory signaling molecules.

Results Caregivers showed marked changes over time in diurnal output of salivary amylase, a marker of SNS activity, whereas secretions in controls were stable during follow-up. Cortisol output was similar in caregivers and controls. During the year, caregivers showed a profound linear increase in systemic inflammation, as indexed by CRP. At the same time, they displayed a linear decline in mRNA for anti-inflammatory signaling molecules and diminished in vitro glucocorticoid sensitivity.

Conclusion These preliminary data show that familial caregivers of patients with cancer experience marked changes in neurohormonal and inflammatory processes in the year after diagnosis. These changes may place them at risk for morbidity and mortality from diseases fostered by excessive inflammation.

Supported by Grant No. 89736 from the Canadian Institutes of Health Research, Grant No. CL-SCH-58 from the Michael Smith Foundation for Health Research (G.E.M., N.R.), and Grant No. RO 2353/4-1 from the German Research Foundation (Deutsche Forschungsgemeinschaft).

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

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