Treatment of the chronic inflammation in peripheral target tissue improves the crushed nerve recovery in the rat: histopathological assessment of the nerve recovery.

An experimental study was performed to investigate the influence of subsidence of chronic inflammation in peripheral target tissue on the recovery of crushed nerve. Seventy-eight male Wistar rats weighing 300-370 g were used. The sciatic nerve was operatively crushed unilaterally with an aneurysm clip (250 gf) applied for 5 min. Chronic inflammation, localized to the ankle, was induced by intra-articular injection of complete Freund's adjuvant 1 week preoperatively. Prednisolone farnesylate (PNF-21) 1.4% gel was applied on the ankle as an anti-inflammatory agent for consecutive days after the operation. The animals were divided into five groups as follows: crush injury with ipsilateral arthritis (CIA); crush injury with ipsilateral arthritis and PNF-21 gel applied on the ipsilateral ankle (CIA + IPNF); crush injury with ipsilateral arthritis and PNF-21 gel applied on the contralateral ankle (CIA + CPNF); crush injury with contralateral arthritis (CCA); crush injury without arthritis (C). Specimens for histopathological examination were taken from the nerve at a site 5 mm distal to the crush lesion at 4 weeks postoperatively. The average axon diameter was significantly larger in the CIA + IPNF group than in the CIA group (p < 0.01). No significant difference was observed between the CIA + CPNF group and the CIA group. In conclusion, chronic inflammation in peripheral target tissue suppresses recovery of the crushed nerve, and subsidence of this chronic inflammation improves this suppression histopathologically.

Systemic immune response in whiplash injury and ankle sprain: elevated IL-6 and IL-10.

Whiplash injury and whiplash-associated disorders (WAD) are significant problems of modern society. Numerous attempts have been made to characterize the nature of whiplash injury. Whether the immune system is involved during the disease process is not known. In a prospective study, using enzyme-linked immunospot (ELISPOT) assays, we examined numbers of blood mononuclear cells (MNC) secreting pro- (IFN-gamma, TNF-alpha, IL-6) and anti-inflammatory (IL-10) cytokines in patients with WAD and, for reference, patients with ankle sprain and multiple sclerosis and healthy subjects. An immune response reflected by elevated numbers of TNF-alpha- and IL-10-secreting blood MNC was observed in patients with WAD examined within 3 days compared to 14 days after the whiplash injury. The patients with WAD examined within 3 days after the injury had also higher numbers of IL-6 and IL-10 secreting blood MNC compared to healthy subjects. The alterations of cytokine profiles observed in WAD were also observed in patients with ankle sprain when examined within 3 days after trauma. In contrast, there were no differences for cytokine profiles between patients with WAD examined 14 days after the whiplash injury and healthy subjects. Relatively minor trauma like WAD and ankle sprain are associated with a systemic dysregulation in numbers of cells secreting pro- as well as anti-inflammatory cytokines.

Biochemical changes after trauma and skeletal surgery of the lower extremity: quantification of the operative burden.

OBJECTIVE: To quantify changes in variables of inflammation, coagulation, and fibrinolysis in blunt trauma patients with lower extremity fractures who underwent different types of surgical procedures. DESIGN: Prospective, cohort study. SETTING: Level I university trauma center. PATIENTS: We allocated 83 blunt trauma patients in stable condition and 22 patients eligible for elective hip replacement to four treatment groups. INTERVENTIONS: In 34 multiply traumatized patients with femoral fracture (group PTFF) and in 28 patients with an isolated femoral fracture (group IFF), primary unreamed intramedullary nailing for stabilization of the femoral shaft fracture was performed. In 22 patients, an elective uncemented total hip arthroplasty (group THA) was inserted for osteoarthritis, and in 21 control patients, an isolated ankle fracture (group AF) was acutely stabilized. MEASUREMENTS AND MAIN RESULTS: From serially sampled central venous blood, the perioperative concentrations of interleukin (IL)-6, of tumor necrosis factor-alpha, of prothrombin fragments 1 + 2, and of D-dimer cross-linked fibrin degradation products were evaluated. Intramedullary instrumentation for an isolated femur fracture caused a significant perioperative increase in the concentrations of IL-6 (preoperative IL-6, 52 +/- 12 pg/mL; IL-6 30 mins postinsertion, 78 +/- 14 pg/mL; p = .02). This increase was comparable with group THA (preoperative IL-6, 46 +/- 16 pg/mL; IL-6 30 mins postinsertion, 67 +/- 11 pg/mL; p = .03). A positive correlation occurred between both groups (r = .83, p < .0004). Multiple trauma patients demonstrated significantly (p = .0002) higher IL-6 concentrations than all other groups throughout the study period and showed a significant increase after femoral nailing (preoperative IL-6, 570 +/- 21 pg/mL; IL-6 30 mins postinsertion, 690 +/- 24 pg/mL; p = .003), whereas no perioperative change was seen in group AF. The highest IL-6 increases were associated with a longer ventilation time (group PTFF) and a longer period of positive fluid balances (groups PTFF, IFF, THA). The coagulatory variables demonstrated similar perioperative increases in groups IFF and THA, but not in groups PTFF and AF. The IL-6 concentrations and the prothrombin fragments 1 + 2 concentrations correlated between groups THA and IFF at 30 mins and at 1 hr after surgery (r2 = .64, p < .02). In all patients the clinical variables were stable perioperatively. CONCLUSIONS: Major surgery of the lower extremity causes changes to the inflammatory, fibrinolytic, and coagulatory cascades in patients with stable cardiopulmonary function. The inflammatory response induced by femoral nailing is biochemically comparable to that induced by uncemented total hip arthroplasty. In multiple trauma patients, increases, which occurred in addition to those induced by the initial trauma, were measured. Definitive primary femoral stabilization by intramedullary nailing imposes an additional burden to the patient with blunt trauma. A careful preoperative investigation is required to evaluate whether primary definitive stabilization can be performed safely.