Mucosal and enterocyte IL-6 production during sepsis and endotoxemia--role of transcription factors and regulation by the stress response.
BACKGROUND
Sepsis and endotoxemia are associated with increased production of interleukin-6 (IL-6) in gut mucosa. Mucosal IL-6 may regulate enterocyte acute phase protein synthesis and intestinal IgA production. In addition, increased IL-6 has been proposed to be a mechanism of loss of mucosal integrity in critical illness. The purpose of this review is to describe current knowledge of the regulation of IL-6 production in the enterocyte/mucosa during inflammation caused by sepsis and endotoxemia.


METHODS
Recent publications describing the influence of sepsis, endotoxemia, and proinflammatory cytokines on mucosal/enterocyte IL-6 production.


CONCLUSIONS
IL-6 production is increased in gut mucosa during sepsis and endotoxemia and in cultured enterocytes after treatment with endotoxin or proinflammatory cytokines. The IL-6 gene is regulated by multiple transcription factors, including NF-kappaB, AP-1, and C/EBP. Because of the multiple important biological roles of IL-6, understanding the cellular and molecular mechanisms of mucosal/enterocyte IL-6 production as well as methods to modulate IL-6 production is of clinical importance in the setting of sepsis and other critical illness.
Pritts
Timothy
T
Department of Surgery, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0558, USA.
Hungness
Eric
E
Wang
Quan
Q
Robb
Bruce
B
Hershko
Dan
D
Hasselgren
Per-Olof
PO
D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D019446:Endotoxemia / Q000503:physiopathology*; D020895:Enterocytes / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018805:Sepsis / Q000503:physiopathology*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D014157:Transcription Factors; D051742:Transcription Factor CHOP