This study confirms that multitrauma patients have a significant inflammatory response measured by plasma levels of IL-6 and PMNs phenotype. Furthermore, patients who developed ALI/ARDS demonstrated severe systemic inflammation measured by plasma IL-6 levels and PMN activation markers. This study is thereby comparable with previous studies which measured plasma cytokine levels and PMN phenotype. In addition, we measured PMN activation towards the innate stimulus fMLP. Active inside-out control of PMNs towards fMLP was significantly decreased in patients with more severe injuries. However, with this sensitive measurement, no additional activation of PMNs occurred after IMN of femur fractures, in either patients with isolated femur fractures or multitrauma patients.
Trauma induces inflammation and severe inflammation has been related to the development of ALI/ARDS . It has been demonstrated that PMNs play an essential role in the pathophysiology of ALI/ARDS, whereas the roles of cytokines (such as IL-6) and monocytes are less clear, because these cytokines often have multiple target cells and different functions. IL-6 levels have often been used for their prognostic importance, but no causal pathophysiological relation has been identified [16, 17]. It is true that more trauma results in more systemic inflammation and thus in more cytokine release. However, IL-6 does not cause damage to the pulmonary endothelium. Products produced by PMNs cause this damage and our data support the importance of PMNs. Severe trauma results in an altered PMN phenotype patients who developed ARDS demonstrated the most activated PMNs. In addition, our study suggest a role for monocytes as well in the pathophysiology of ALI/ARDS. Monocyte HLA-DR expression was decreased in multitrauma patients, indicating a more pro-inflammatory type of monocytes which has been suggested previously to contribute to the tissue damage during a systemic inflammatory response.
We next studied the impact of intramedullary nailing on the systemic inflammatory response. Additional inflammation caused by surgery is seen as additional trauma and has been considered as a possible risk factor for organ failure such as ARDS . Much to our surprise the increased damage caused by IMN only partly induced changes in the systemic inflammatory response (only monocyte HLA-DR expression in patients with isolated femur fractures). Most striking was the absence of additional PMN activation after intramedullary nailing. This lack of change in PMN phenotype during IMN is in line with suggestions from a previously published report . In that cohort, no increase was seen in MAC-1 expression on PMNs after bilateral femur fracture fixation. Thus, the extend of PMN activation appears mainly determined by the severity of initial trauma and is apparently not altered by intramedullary nailing. In contrast, plasma IL-6 levels and monocyte HLA-DR were significantly altered by intramedullary nailing. Thus, an impact of the surgical procedure can be measured by cytokines and the monocyte compartment.
The blood samples were taken 1 hour prior to IMN and 18 hours after IMN, regardless of the interval between trauma and surgery. Although this affects the reproducibility of the results, it reflects daily care practice. 18 hours after IMN the peak of plasma IL-6 levels will be passed (max at 6 hours post-operatively), but the changes in PMN phenotype will be most defined. PMN phenotype behaved similarly in all patients, therefore, 38 patients were sufficient to state the conclusion.
Because we analyzed the functional phenotype of PMNs and monocytes, more information was obtained than merely static phenotypes. The inflammatory cellular response deficit to the development of ARDS appears to be mainly determined by the initial injuries and not the additional insult by IMN.