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

Hideyuki Nukina, Nobuyuki Sudo, Yuhji Aiba, Naomi Oyama, Yasuhiro Koga, Chiharu Kubo

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)


Several recent reports demonstrated that restraint stress elevates plasma IL-6 levels; however, the precise mechanism whereby stress stimuli trigger the production of IL-6 remains to be clarified. In this study, in order to elucidate whether or not the intestinal microflora contribute to the stress-induced IL-6 elevation, the plasma IL-6 response of germ-free (GF) mice, which are indeed devoid of indigenous microflora, was compared to that of specific 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 in SPF mice. In addition, such a stress-induced IL-6 elevation was also found in the mice reconstituted with SPF feces. The expression levels of IL-6 mRNA in the liver increased after 1 h of stress in both GF and SPF mice based on the findings of a semiquantitative RT-PCR method, although no such increase was observed in the spleen and kidney of both groups of mice. These results thus indicate that restraint stress is capable of elevating the plasma IL-6 levels independently of the intestinal microflora and the liver is one of the main sources responsible for the increased plasma IL-6 during stress.

Original languageEnglish
Pages (from-to)46-52
Number of pages7
JournalJournal of Neuroimmunology
Issue number1-2
Publication statusPublished - Apr 2 2001

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology


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