OBJECTIVES-This study examined whether chronic interpersonal stress is associated with cellular markers of inflammation and regulation of these responses by in vitro doses of glucocorticoids in rheumatoid arthritis (RA) patients. The association between these markers of inflammation and fatigue was also tested.METHODS-Fifty-eight RA patients completed up to 30 daily ratings of the stressfulness of their interpersonal relations. Interleukin-6 (IL-6) production was analyzed in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cell cultures with and without varying concentrations of the glucocorticoid hydrocortisone. In addition, plasma levels of IL-6 and C-reactive protein (CRP) were analyzed, and subjective ratings of fatigue and pain were obtained on the day of blood sampling, RESULTS-Multilevel modeling showed that higher chronic interpersonal stress was associated with greater stimulated IL-6 production (p < 0.05) as well as greater resistance to hydrocortisone inhibition of IL-6 production (p < 0.05). These relations were not accounted for by demographic factors, body mass index, or steroid medication use. Stimulated production of IL-6, in turn, was associated with greater levels of self-reported fatigue, controlling for pain (p < 0.05). Neither chronic stress ratings nor fatigue symptoms were related to plasma levels of IL-6 or CRP (p's >.05).CONCLUSIONS-Among RA patients, chronic interpersonal stress is associated with greater stimulated cellular production of IL-6 along with impairments in the capacity of glucocorticoids to inhibit this cellular inflammatory response. Moreover, these findings add to a growing body of data that implicate heightened proinflammatory cytokine activity in those at risk for fatigue symptoms.

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Objective-Monocyte proinflammatory activity has been demonstrated in obesity, insulin resistance, and type 2 diabetes, metabolic conditions that are frequently associated with elevated levels of nonesterified fatty acids (NEFA). We therefore tested the hypothesis that NEFA may induce monocyte inflammation. Methods and Results-Monocytes exposed to NEFA for 2 days demonstrated a dose-related increase in intracellular reactive oxygen species (ROS) formation and adhesion to endothelial cells. All of these effects were inhibited by the coaddition of antioxidants such as glutathione or butylated hydroxytoluene, by inhibition of ROS generation by NADPH oxidase inhibitors, and by inhibition of protein kinase C, a recognized stimulator of NAPDH oxidase.

CD40-CD40 ligand interactions play an essential role in T cell/B cell collaboration. The data presented in this review have served to widen the scope of CD40-CD40 ligand interactions to include initial activation, proliferation, differentiation, and isotype switching of B cells, as well as subsequent downregulation of B cell function. Moreover, CD40 ligand expression by activated B cells is likely to play an essential role in facilitating ongoing responses of stimulated B cells maturing in germinal centers. Finally, CD40 expression by activated T cells may also play an important role in regulating the function of helper T cells within germinal centers. In summary, emerging data have expanded the role of CD40-CD40 ligand interaction during T cell/B cell collaboration and have emphasized its potential to regulate many of the functions of both partners in this essential interaction involved in antibody production.