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

Abstract

BackgroundTLR-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.MethodsMale 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.ResultsPre-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).ConclusionsAfter 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.

The Influence of Macrophage-Activating Lipopeptide 2 (MALP-2) on Local and Systemic Inflammatory Response in a Murine Two-Hit Model of Hemorrhagic Shock and Subsequent Sepsis

“…Thus, observations reported by Pfeifer et al . were confirmed [ 9 ]. Also, Feterowski et al described no elevation of IL-10 after systemic injection of MALP-2 in mice.…”

“…Thus, our findings are in line with data published by Zeckey et al who also did not observe a significant impact of MALP-2 on pro-inflammatory mediator levels (IL-6, TNF-α, and MIP-1α) 96 h after induction of isolated sepsis [ 10 ]. In a murine model of isolated TH, Pfeifer et al found that MALP-2 application before the insult resulted in a more balanced migration of PMN into different body compartments instead of accumulating in one [ 9 ]. Based on this finding, it might be speculated that a similar phenomenon is also applicable for immunocompetent cells after the MALP-2 application.…”

“…However, literature regarding the aforementioned association between MALP-2 and MPO-activity is inconsistent. While some studies found that MALP-2 itself induces neutrophil infiltration into the lung and liver tissue [24,25], Pfeifer et al found that pretreatment with MALP-2 before the induction of shock did not have much of an effect on the MPO activity of the lung [9]. However, Pfeifer et al terminated the experiment 6 h after the induction of shock.…”

“…So far, the relevance of MALP-2 treatment has only been investigated after isolated insults. Pfeifer et al found that pre-treatment with MALP-2 resulted in a significant decrease in systemic IL-6 levels in a murine model of isolated hemorrhagic shock [ 9 ]. Zeckey et al demonstrated that MALP-2 could improve survival and reduce systemic cytokine levels in a murine CLP model [ 10 ].…”

Helping prometheus: liver protection in acute hemorrhagic shock

“…Injuries to large vessels cause hypovolemia and generalized ischemia. This leads to microcirculatory disturbances, metabolic changes, and depression of the immune system (1)(2)(3)(4)(5). In addition, it is associated with low organ perfusion and an imbalance between O 2 demand and O 2 supply (6).…”