Restraint stress elevates the plasma interleukin-6 levels in germ-free mice

Several recent reports demonstrated that restraint stress elevates plasma I L-6 levels; however, the precise mechanism whereby stress stimuli trigger t he production of IL-6 remains to be clarified. In this study, in order to e lucidate whether or not the intestinal microflora contribute to the stress- induced IL-6 elevation, the plasma IL-6 response of germ-foe (GF) mice, whi ch an indeed devoid of indigenous microflora. was compared to that of speci fic pathogen-free (SPF) mice. The plasma IL-6 level increased after 1 h of restraint stress and thereafter gradually decreased in GF mice as well as i n SPF mice. In addition, such a stress-induced IL-6 elevation was also foun d in the mice reconstituted with SPF feces. The expression levels of IL-6 m RNA in the liver increased after 1 h of stress in bath GF and SPF mice buse d on the findings of a semiquantitative RT-PCR method, although no such inc rease was observed in the spleen and kidney of both groups of mice. These results thus indicate that restraint stress is capable of elevating t he plasma IL-6 levels independently of the intestinal microflora and the li ver is one of the main sources responsible for the increased plasma IL-6 du ring stress. (C) 2001 Elsevier Science B.V. All rights reserved.