Inflammatory cytokines levels following various fracture patterns among patients managed at Moi Teaching and Referral Hospital, Eldoret, Kenya

Abstract

Background: Inflammatory cytokines are signaling molecules secreted by immune cells that mediate body’s response to injury. Trauma stimulates an inflammatory response which when heightened results in undesirable outcomes like systemic inflammatory response syndrome, adult respiratory distress syndrome, multi-organ failure and death. Accurate quantification of this inflammatory response would enable better injury grading, appropriate timing of surgery, improve patient outcome and prevention of life threatening complications. The inflammatory response following various common fractures has hitherto not been quantified. Objective: To evaluate the levels of inflammatory cytokines, vital signs and complete blood count parameters following various fracture patterns among patients managed at Moi Teaching and Referral Hospital. Methods: A cross-sectional study conducted at MTRH between 1st April 2017 and 31st March 2019. A total of 70 adult participants comprising of 56 patients with fractures and 14 age and gender matched negative controls were studied. The patients with fractures were divided into 4 groups of 14 subjects each based on the fractured bone as follows: isolated femur fracture (F), isolated tibial fracture (T), isolated upper limb fractures (UL), and polytrauma patients (P). The control group (C) comprised of 14 age and gender matched healthy individuals without fractures. Systematic sampling was used to pick the 56 participants out of approximately 1,200 patients with fractures seen at MTRH annually. Fractures were evaluated for number, pattern, extent of soft tissue involvement and whether they were open or closed. Grading was subsequently done using the Abbreviated Injury Score (AIS) or the New Injury Severity Score (NISS). Flow-Cytometry Bead Assay was used to analyse IL-1β, IL-6, IL-8, IL-10 and TNF-α levels. In addition, patients’ vital signs and complete blood count (CBC) were captured. Data was summarised as mean ± SD and presented using tables and scatter plots. One-way analysis of variance used to compare the means of the different study groups. Spearman’s rank correlation tests were used to check for association between the variables. Results: The fracture groups had higher mean IL-6 levels with the polytrauma group recording the highest levels: 181.4 ± 188.7 (P); 127.8 ± 28.6 (UL); 89.5 ± 140 (T); 106.9 ± 84.0 (F); and (12.4 ± 6.8 (C) pg/mL; p = 0.005). The fracture groups had higher mean IL-8 levels with the polytrauma group recording the highest levels: 126.4 ± 103.9 (P); 81.0 ± 48.8 (UL); 58.8 ± 37.3 (T); 83.1 ± 53.1 (F); (40.0 ± 30.4 (C) pg/mL; p = 0.004). There was positive correlation between IL-6 levels and fracture pattern severity (r = 0.509, p = 0.001), soft tissue injury (r = 0.577, p = 0.001), presence of open fractures (r = 0.593, p = 0.001), AIS (r = 0.636, p = 0.001) and NISS (r = 0.753, p< 0.001). The fracture groups had lower mean platelet counts (328.73 ± 55.4 (C); 211 ± 23 (UL); 227.15 ± 58.3 (T); 243 ± 105.4 (F); 96.2 ± 33.7 (P) X 109/L; p= 0.001). The polytrauma group (P) had statistically significant higher pulse rate, respiratory rate and shock index than the negative control group (C) (p < 0.01).There was inverse correlation between IL-6 and platelet count (r = -0.252, p = 0.05). Conclusion: The IL-6 and IL-8 levels were elevated in fracture patients being highest in patients with polytrauma. There was inverse correlation between platelet count and both IL-6 and IL-8 levels. There was positive correlation between shock index and both IL-6 and IL-8. Recommendation: Adoption of the use of inflammatory cytokines to improve trauma patients’ stratification, determine best time for surgery and to refine existing trauma scores. In addition, the study recommends the use of platelet count as an alternate measure of inflammation following trauma.