title: Inflammatory responses to psychological stress in fatigued breast cancer survivors: relationship to glucocorticoids.
abstract: Fatigue is a common problem following cancer treatment and our previous studies suggest that a chronic inflammatory process might contribute to cancer-related fatigue. However, immune responses to challenge have not yet been evaluated among individuals with cancer-related fatigue, and it is not known what mechanisms drive increased levels of inflammatory markers in fatigued cancer survivors. We have previously reported that fatigued breast cancer survivors show a blunted cortisol response to an experimental psychological stressor. In this report, we focus on inflammatory responses to this stressor and their relationship to circulating glucocorticoids and cellular sensitivity to glucocorticoid inhibition. Relative to non-fatigued control survivors, participants experiencing persistent fatigue showed significantly greater increases in LPS-stimulated production of IL-1beta and IL-6 following the stressor (Group x Time interaction: p<.05). Fatigued participants did not show any difference in cellular sensitivity to cortisol inhibition of cytokine production, but they did show significantly less salivary cortisol increase in the aftermath of the stressor. Moreover, blunted cortisol responses were associated with significantly increased production of IL-6 in response to LPS stimulation (p<.05). These data provide further evidence of enhanced inflammatory processes in fatigued breast cancer survivors and suggest that these processes may stem in part from decreased glucocorticoid response to stress.
authors.affiliation: Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience at UCLA, 300 UCLA Medical Plaza, Room 3306, Box 957076 Los Angeles, CA 90095-7076, USA. jbower@ucla.edu
authors.forename: Julienne E
authors.initials: JE
authors.lastname: Bower
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.forename: Najib
authors.initials: N
authors.lastname: Aziz
authors.forename: Richard
authors.initials: R
authors.lastname: Olmstead
authors.forename: Michael R
authors.initials: MR
authors.lastname: Irwin
authors.forename: Steve W
authors.initials: SW
authors.lastname: Cole
mesh_terms: D000208:Acute Disease; D000368:Aged; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D005221:Fatigue / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D017741:Survivors
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D006854:Hydrocortisone