MALP-2 pre-treatment modulates systemic inflammation in hemorrhagic shock

BACKGROUND: TLR-2 is expressed on the surface of leucocytes, lung and liver tissue and initiates the activation of immune response after interaction with components of the bacterial cell wall. In this experiment we investigated whether immunostimulation with TLR-2 agonists under conditions of sterile inflammation (hemorrhagic shock (HS)) may affect the immune response and remote organ inflammation. METHODS: Male C57/BL6 mice were subjected to standardized pressure-controlled HS (MAP of 35 mmHg for 90 minutes). The TLR-2 agonist macrophage-activated lipopeptide-2 (MALP-2) was administered (i.p.) either 12 hours prior to the induction of HS (Group MALP PT) or after the hypotensive period (90 minutes) (Group MALP T). After six hours, plasma cytokine levels (IL-6, KC, IL-10, and MCP-1) and lung and liver MPO activity were assessed. RESULTS: Pre-treatment with MALP-2 resulted in a significant attenuation of the systemic pro-inflammatory (IL-6) response (MALP PT: 0.83±0.2 ng/ml vs. MALP T: 1.7±0.09 ng/ml) (p<0.05). In comparison to the liver MPO activity, lung MPO levels in in group MALP PT did not show differences to levels measured in MALP T mice (1.200±200 ng/mg vs. 1.800±200 ng/mg). CONCLUSIONS: After initial inflammation, MALP-2 pre-treatment was associated with attenuated systemic immune response after sterile stimulus. The TLR-2 agonist appears to affect sterile inflammation pathways. The exact mechanisms should be studied further to better understand these affects.