Stress activation of cellular markers of inflammation in rheumatoid arthritis: protective effects of tumor necrosis factor alpha antagonists.
OBJECTIVE
Psychological stress is thought to aggravate disease activity in rheumatoid arthritis (RA), although the physiologic mechanisms are unclear. Tumor necrosis factor alpha (TNFalpha) is an inflammatory cytokine involved in the exacerbation of RA, and TNFalpha antagonists have emerged as efficacious treatments. The purpose of this study was to determine whether RA patients show increased monocyte production of TNFalpha following acute psychological stress and whether such responses are abrogated in RA patients taking TNFalpha antagonists.


METHODS
A standardized stress task was administered to 3 groups of subjects: RA patients taking TNFalpha antagonists, RA patients not taking such medications, and healthy controls. Lipopolysaccharide-stimulated monocyte production of inflammatory cytokines was repeatedly measured using intracellular staining and flow cytometry. Subjective stress, cardiovascular responses, adrenocorticotropic hormone (ACTH) levels, and cortisol levels were also measured.


RESULTS
The stress task induced increases in subjective stress, cardiovascular activity, and levels of ACTH and cortisol, with similar responses in the 3 groups. In addition, the stress task induced a significant increase (P < 0.001) in monocyte production of TNFalpha among RA patients who were not taking TNFalpha antagonists. However, monocyte production of TNFalpha did not change following psychological stress in RA patients taking TNFalpha antagonists or in healthy controls.


CONCLUSIONS
Brief psychological stress can trigger increased stimulated monocyte production of TNFalpha in RA patients. The use of TNFalpha antagonists protects against stress activation of cellular markers of inflammation in RA patients.
Motivala
Sarosh J
SJ
UCLA Semel Institute for Neuroscience and Human Behavior, Cousins Center for Psychoneuroimmunology, University of California, Los Angeles 90095-7076, USA. smotivala@mednet.ucla.edu
Khanna
Dinesh
D
FitzGerald
John
J
Irwin
Michael R
MR
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000276:immunology; D013315:Stress, Psychological / Q000150:complications* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D018501:Antirheumatic Agents; D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000324:Adrenocorticotropic Hormone; D002097:C-Reactive Protein; D006854:Hydrocortisone