IL-6 rescues enterocytes from hemorrhage induced apoptosis in vivo and in vitro by a bcl-2 mediated mechanism

Following a hemorrhagic event, damage to the highly metabolic intestinal ti ssue induces loss of barrier function leading to bacterial escape and LPS c ontamination of the host. Orally administered IL-6 restores intestinal barr ier function following hemorrhage in both rat and mouse models, IL-6 preven ts apoptosis in a variety of lymphoid cells and lines, through the activati on of the proto-oncogene bcl-2. This communication elucidates the role of t he IL-6-bcl-2 interaction in intestinal apoptosis following hemorrhagic sho ck. Terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling ( TUNEL) and p53 immunohistochemical staining were used to examine intestines from mice hemorrhaged and fed saline or IL-6 and enterocytes (IEC-6) expos ed to hypoxia and LPS alone or LPS and IL-6 in vitro. bt situ hybridization for bcl-2 expression was performed on intestines or enterocytes, Intestina l sections from mice hemorrhaged and fed IL-6 showed reduction in apoptosis and increases in bcl-2 gene expression relative to sections taken from mic e hemorrhaged and fed saline. IEC-6 cells exposed to hypoxia and LPS had hi gh numbers of TUNEL staining cells. Subsequent exposure to IL-6 after hypox ia and LPS reduced apoptotic cell numbers and increased bcl-2 gene expressi on, The data show that exposure of intestinal epithelial cells to IL-6 eith er by oral administration in hemorrhaged mice or by coculture following hyp oxia and LPS treatment results in increased bcl-2 gene expression and reduc ed damage from apoptosis. (C) 1998 Academic Press.