Stress activation of cellular markers of inflammation in rheumatoid arthritis: Protective effects of tumor necrosis factor α antagonists




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


A standardized stress task was administered to 3 groups of subjects: RA patients taking TNFα 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.


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 TNFα among RA patients who were not taking TNFα antagonists. However, monocyte production of TNFα did not change following psychological stress in RA patients taking TNFα antagonists or in healthy controls.


Brief psychological stress can trigger increased stimulated monocyte production of TNFα in RA patients. The use of TNFα antagonists protects against stress activation of cellular markers of inflammation in RA patients.