Hemorrhage-induced intestinal damage is complement-independent in Helicobacter hepaticus-infected mice.

With more than half of the world population infected, Helicobacter infection is an important public health issue associated with gastrointestinal cancers and inflammatory bowel disease. Animal studies indicate that complement and oxidative stress play a role in Helicobacter infections. Hemorrhage (HS) induces tissue damage that is attenuated by blockade of either complement activation or oxidative stress products. Therefore, we hypothesized that chronic Helicobacter hepaticus infection would modulate HS-induced intestinal damage and inflammation. To test this hypothesis, we examined HS-induced jejunal damage and inflammation in uninfected and H. hepaticus-infected mice. Helicobacter hepaticus infection increased HS-induced midjejunal mucosal damage despite attenuating complement activation. In addition, infection alone increased chemokine secretion, changing the HS-induced neutrophil infiltration to a macrophage-mediated inflammatory response. The HS-induced macrophage infiltration correlated with increased secretion of tumor necrosis factor-α and nitric oxide in the infected mice. Together, these data indicate that Helicobacter infection modulates the mechanism of HS-induced intestinal damage and inflammation from a complement-mediated response to a macrophage response with elevated tumor necrosis factor-α and nitric oxide. These data indicate that chronic low-level infections change the response to trauma and should be considered when designing and administering therapeutics.