| Objectives:1.To evaluate the effectiveness of IL-6(Interleukin 6,IL-6)for preoperative diagnosis of infection in patients with nonunions.2.To provide a new implant-related infected model after intramedullary fixation of the femur in rats.3.To evaluate the utility of IL-6 in the implant-related infected rat model.Methods:1.Forty-two patients suspected with infected nonunion were investigated in the study.The levels of white blood-cell count(WBC),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and interleukin-6(IL-6)were measured.A positive diagnosis of infection was made on the basis of the positive culture results.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of each test were calculated.2.All animals were created an oblique fracture of the midshaft femur and stabilized with intramedullary nail.Two groups were tested:group 1:no bacterial contamination at fracture site(15 rats),group 2:all rats were contaminated with 10~7colony forming units(CFU)of Staphylococcus aureus(15 rats).All animals were sacrificed after 56 days and the degree of bone healing and infection were evaluated by clinically observation,X-ray,micro-CT scanning,histology analysis and bacterial culture.3.Blood samples were collected from the abdominal aortic on day 1,2,3,4,5,6,7 and week 2,3,4,5,6,7,8.After collected blood samples,the rats were immediately sacrificed and anatomical dissection was performed in sterile condition and the bone were harvested for bacterial culture.The serum level of IL-6 were determined by Elisa test and WBC were detected by an automatic cell counter(MEK-6450K).Results:1.The test of WBC had the highest specificity(85.7%,95%confidence interval[CI]:42.01-99.25),but lowest sensitivity(22.9%,95%CI:11.04-40.55).The sensitivity and specificity of CRP were both higher than IL-6:60.0%versus57.1%and 85.7%versus 57.1%,respectively.With one,two,three and four positive tests,the predicted probabilities of infection were 66.7%,90.9%,100%,and 100%,respectively,but the number of patients who had three or four positive tests were small.2.All rats were survived after surgery and the surgical incision were healed in two weeks without infected signs.The body weight of experimental group rats were significantly lower than control group rats on day 14(P<0.05)and statistical difference of body temperature were find after surgery of 2,4,6 and 8 days(P<0.05).In S.aureus group,the cortical bone reaction and osteolysis were found by X-Ray and micro-CT about13 of 15 rats(86.7%)and showed uncompleted bone healing after 56 days.Odekerken's Osteomyelitis grading score significantly differed from the control group(P<0.05).These rats also showed positive histology and microbiological infection signs.In control group,all rats achieved a complete bone healing and no positive infection evidences was found.3.In the acute phase of infection,the response of WBC was found a time lag after infection.Three days after infection,the rats in experimental group showed a significant increase of WBC to the control group rats.IL-6 presented more sensitive response for infection and a significant difference was found after surgery.Although,there was no significant difference was found on days 5 after surgery,the level of IL-6 was also significant increase to the control group.Conclusion:1.The diagnostic utility of IL-6 is inferior to CRP and is not an effective screening marker for the presence of infected nonunion.2.Our study provided a new animal model of implant-related infection in rats and the model accurately mimics the clinical situation.3.IL-6 is a sensitive marker in the acute phase of infection,however,as infection time increases,the utility of IL-6 display a decrease change. |
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