Early immune system activation at the systemic level initiates in the liver in experimental compensated cirrhosis
- Ubeda, M.
- Munoz, L.
- Nieto, M.
- Lario, M.
- Diaz, D.
- Lledo, L.
- Monserrat, J.
- Reyes, E.
- Sanz, E.
- De-la-Hera, A.
- Alvarez-Mon, M.
- Albillos, A.
ISSN: 0168-8278
Year of publication: 2008
Volume: 48
Pages: S106
Congress: 43rd Annual Meeting of the European Association for the Study of the Liver. 23 April 2008 - 27 April 2008
Type: Conference Poster
Abstract
Background: Gut bacterial translocation leads to immune system activation in cirrhosis with ascites (Mu˜noz L et al. Hepatology 2005; 42: 411).Enteric bacteria reach the mesenteric lymph nodes and activate resident immune-system cells; later, recirculation of these activated immune cells extends inflammation to the systemic circulation. However, in compensated cirrhosis, in which gut bacterial translocation is unlikely, it is unknown whether immune activation occurs at the systemic level, and the potential contribution of the liver, as the target organ of inflammation in cirrhosis, is also unclear. Aims: To determine in compensated cirrhosis (without ascites): (1) the activation status of the immune system in peripheral blood, liver, and liverdraining (LLN) and mesenteric lymph nodes (MLN), and (2) the contribution of these systems, if any, to systemic inflammation. Methods and Results: Protocol I: The activation status of immune cells was assessed by flow cytometry in rats with compensated cirrhosis (induced by gavage CCl4, 12 wk) and controls. Inflammation occurred at the systemic level in cirrhotic rats, as shown by the expansion (p<0.05) in peripheral blood of infiltrating monocytes (1.9-fold controls), recently activated Th cells (Th-r) (5.9-fold) and non-terminated effector memory Th cells (Th-m) (1.7-fold). The cirrhotic liver showed expansion (p<0.05) of infiltrating monocytes (1.4-fold) and Th-r cells (4.8-fold). The number of Th-r, Th-m and monocytes was elevated (p<0.05) in the LLN and MLN of cirrhotic rats. Th-cells were locally activated in LLN and MLN, as shown by the expansion in these territories of CD62L–Th-cells. In cirrhotic rats, systemic inflammation, defined by the circulating number of TH-m cells, correlated with inflammation in LLN (r=0.74, p<0.05), but not in MLN. Protocol II: Cirrhotic rats were administered non-absorbable antibiotics or placebo to examine the contribution of enteric bacteria to systemic inflammation. Treatment normalized Th-m, inflammatory monocytes and dendritic cell numbers in MLN, but not in peripheral blood or LLN. Conclusion: Systemic activation of the immune system is an early event in experimental compensated cirrhosis. Such activation is initiated in the liver draining lymph nodes and, unlike the case in cirrhosis with ascites, is independent of gut bacterial translocation.