Abstract
In polytrauma patients, the impact of splenectomy is equivocal, ranging from negative to protective. We investigated the impact of splenectomy on immune responses in the 1st-hit polytrauma alone and on survival in the post-traumatic sepsis (2nd hit). Female BALB/c mice underwent polytrauma (1st hit) consisting of either a) TH: femur fracture, hemorrhagic shock or b) TSH: splenectomy, femur fracture, hemorrhagic shock. Additionally, the polytrauma hit was followed by cecal ligation and puncture (CLP) 48 h later and compared to CLP alone. Splenectomy improved the 28-day survival in secondary sepsis to 92% (from 62%), while TH lowered it to 46% (p < 0.05). The improved survival was concurrent with lower release of inflammatory cytokines (IL-6, CXCL-1, MCP-1) and increase of C5a post-CLP. In the polytrauma hit alone, TSH induced stronger neutrophilia (1.9 fold) and lymphocytosis (1.7 fold) when compared to TH mice. Moreover, TSH resulted in a 41% rise of regulatory T-cells and reduced the median fluorescence intensity of MHC-2 on monocytes by 55% within 48 h (p < 0.05). Conversely, leukocyte phagocytic capacity was significantly increased by 4-fold after TSH despite a similar M1/M2 macrophage profile in both groups. Summarizing, splenectomy provoked both immuno-suppressive and immuno-stimulatory responses but was life-saving in secondary sepsis. Additionally, the polytrauma components in 2-hit models should be tested for their effects on outcome; the presumed end-effect of the 1st hit solely based on the common immuno-inflammatory parameters could be misleading.
Highlights
Polytraumatized patients typically develop a systemic immune reaction, termed systemic inflammatory response syndrome (SIRS), accompanied by the compensatory anti-inflammatory response syndrome (CARS), which can result in a dysfunctional host immune response and predispose them for secondary infections and sepsis[1,2,3]
To uncover whether the cellular and functional changes of the innate and adaptive immunity caused by splenectomy in the polytrauma model affect the 28-day survival rate of secondary sepsis, mice were subjected either to a combination of Trauma-hemorrhage model (TH) or traumatic-hemorrhagic shock combined with splenectomy (TSH) with Cecal ligation and Puncture (CLP) 48 h later or to CLP alone (Fig. 1)
Additional splenectomy in the TSH hit resulted in a survival rate of 92% (p < 0.05 compared to TH-CLP) at day 28 post-CLP (Fig. 2)
Summary
Polytraumatized patients typically develop a systemic immune reaction, termed systemic inflammatory response syndrome (SIRS), accompanied by the compensatory anti-inflammatory response syndrome (CARS), which can result in a dysfunctional host immune response and predispose them for secondary infections and sepsis[1,2,3]. Strong immunosuppressive features coexisted with clear signs of post-traumatic immune activation; e.g. Sturm et al showed a partially increased phagocytosis with simultaneously decreased antigen presenting capacity of PMNs in trauma patients (ISS > 28) compared to healthy controls[16]. A number of recent studies demonstrated that more severe polytrauma models including blunt chest trauma[28], traumatic brain injury[29] and burns[30] appear to better recapitulate the immunologic and genomic responses observed in human polytrauma patients[31]. Their conclusions were typically based on results from ex-vivo tests[32,33,34]. Our data show that additional splenectomy strongly improved long-term outcome after secondary septic insult by modifying various immuno-inflammatory responses after polytrauma
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