Small intestine inflammation in rats with CCL4 cirrhosis: role of enteric bacteria

Resumen

Increases in enteric bacterial load and intestinal permeability are among the factors that promote bacterial translocation to the mesenteric lymph nodes (MLN) in cirrhosis. The effect of these factors on intestinal intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) has not yet been addressed in cirrhosis. T-cell activating and trafficking to the gut have been incriminated in the increased intestinal permeability observed in chronic inflammatory bowel conditions. Aims: To study: i. the distribution and activation status of T-cells and monocytes/ macrophages in IELs and LPLs in cirrhotic rats, and ii. the contribution of luminal enteric bacteria to the observed abnormalities. Methods: Small intestinal IELs and LPLs were isolated from rats with CCl4-cirrhosis (n=18), controls (n=8), and cirrhotic rats after bowel decontamination with antibiotics (n=6). Cell populations were identified by four-colour flow cytometry. Gut bacterial translocation was defined as MLN culture positivity. Results: Compared with controls, cirrhotic rats showed increased (p<0.01) numbers (cells/cm small intestine) of T-cells (174781±73443 vs 105826±27346) and monocytes/macrophages (CD11bbright+CD3−CD45RA−NKR-P1Abright−) (11438±6723 vs 4368 ±1858) among LPLs. This T-cell expansion affected both Th(CD3+CD4+) (1.5-fold) and Tc- (CD3+TCRab+CD8ab+) (3.5-fold) LPLs. T-cells from LPLs showed signs of activation, including increased numbers of recently activated Th-cells (CD3+CD4+CD134+) and NKTcells (CD3+NKR-P1A+). Besides, LPLs from cirrhotic rats showed a higher (p<0.05) frequency of IFNg-secreting Th- (34±5% vs 24±1%) and Tc-cells (58±8% vs 37±2%). In addition, LPLs from cirrhotic rats showed a marked (p<0.01) increase in regulatory populations, such as gdT-cells (CD3+TCRgd+) (6.0-fold) and Treg (CD3+CD4+CD25+FoxP3+) (2.3-fold). The IELs of cirrhotic rats showed similar behaviour. Intestinal mucosal immune activation was more intense in cirrhotic rats showing bacterial translocation (72%). Gut decontamination significantly reduced the faecal load of aerobic bacteria and signs of T-cell activation in the intestinal mucosa of cirrhotic rats. Conclusions: Cirrhosis is associated with a state of immune activation of the intestinal mucosa, which is probably induced by persistent enteric bacterial pressure. The adequate response of immunoregulatory mechanisms maintains mucosal inflammation at the subclinical level. (Resumen completo publicado en: The International Liver Congress™ 2011 Abstract Book. J Hepatol 2011;54:S247).