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DOI: 10.1055/s-0029-1247908
Role of p38 MAPK in trauma-hemorrhage and subsequent pneumococcal pneumonia
Aims: Poly-traumatized patients surviving the initial insult are highly susceptible to secondary pneumonia, frequently progressing into sepsis and multi-organ failure. However, the underlying mechanism of post-traumatic immune suppression is poorly understood.
Methods/Results: Here, we investigated the role of MAPK signalling for the development of impaired lung innate defense in a two-hit model of trauma/hemorrhage (T/H) and subsequent pneumonia. Trauma was induced by midline laparotomy, followed by cannulation of femoral arteries and veins to induce hemorrhage in mice. Subsequently, mice were infected with S. pneumoniae. In the lungs of mice subjected to T/H, a significant increase of p38 MAPK activation was observed. In parallel, we observed increased bacterial loads in the lungs of T/H mice infected with S. pneumoniae, reflective of innate immune suppression in these mice. Interestingly, mice subjected to T/H followed by immediate inhibition of p38 MAPK responded with an improved bacterial pathogen elimination compared to control groups. Moreover, elevated levels of creatinine were also significantly reduced in T/H mice treated with p38 MAPK inhibitor. In addition, p38 inhibition significantly decreased cytokine levels in plasma (IL-6, TNFα, IL-10) of T/H mice.
Summary: Trauma/hemorrhage triggers strong p38 MAPK activation in the lung, which may contribute to post-traumatic immune suppression in mice. p38 MAPK inhibition immediately after T/H decreases inflammatory responses and organ damage and improves lung protective immune responses to bacterial challenge.