IL-6 is essential for development of gut barrier dysfunction after hemorrhagic shock and resuscitation in mice.
We sought to determine the role of IL-6 as a mediator of the alterations in gut barrier function that occur after hemorrhagic shock and resuscitation (HS/R). C57Bl/6 wild-type (WT) and IL-6 knockout (KO) mice on a C57Bl/6 background were subjected to either a sham procedure or HS/R. Organ and tissue samples were obtained 4 h after resuscitation. In WT mice, HS/R significantly increased ileal mucosal permeability to fluorescein isothiocyanate-labeled dextran (average molecular mass, 4 kDa) and bacterial translocation to mesenteric lymph nodes. These alterations in gut barrier function were not observed in IL-6 KO animals. HS/R increased ileal steady-state mRNA levels for IL-6, TNF, and IL-10 in WT but not in IL-6 KO mice. Ileal mucosal expression of the tight junction protein, ZO-1, decreased after HS/R in WT but not IL-6 KO mice. Collectively, these data support the view that expression of IL-6 is essential for the development of gut barrier dysfunction after HS/R.
Yang
Runkuan
R
Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Han
Xiaonan
X
Uchiyama
Takashi
T
Watkins
Simon K
SK
Yaguchi
Arino
A
Delude
Russell L
RL
Fink
Mitchell P
MP
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D019108:Tight Junctions / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D008565:Membrane Proteins; D016753:Interleukin-10; D000410:Alanine Transaminase