Interleukin-6 and Tumor Necrosis Factor-α Production After Acute Psychological Stress, Exercise, and Infused Isoproterenol: Differential Effects and Pathways

OBJECTIVE: The aim of the study was to assess the effects of three different methods of acute activation of the sympathetic nervous system on lipopolysaccharide-induced in vitro production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). METHODS: Thirty-two healthy volunteers performed speech and exercise tasks and underwent a 30-minute infusion of isoproterenol. RESULTS: As expected, acute activation of the sympathetic nervous system led to leukocytosis, including increases in lymphocyte, monocyte, and granulocyte populations (p values <.05). Lipopolysaccharide-induced IL-6 production was increased after both the speaking and exercise tasks (p values <.001), whereas TNF-alpha production was elevated only after exercise (p<.05). In contrast, infusion of isoproterenol inhibited TNF-alpha production (p<.001) and caused no change in IL-6 production. CONCLUSIONS: In response to the challenges, IL-6 and TNF-alpha production showed different profiles. Purely beta-agonist stimulation led to downregulation of TNF-alpha production, providing evidence of the antiinflammatory effect of in vivo beta-receptor activation. The enhanced production of both cytokines after exercise, and of IL-6 after the speech task, can be best explained by a simultaneous upregulation of proinflammatory and inflammation-responding mediators. These effects may have an important role in controlling the immune response to acute psychological and physical stress.