Abstract
BackgroundShunt infection is a frequent and serious complication in the surgical treatment in hydrocephalus. Previous studies have shown an attenuated immune response to these biofilm-mediated infections. We proposed that IL-10 reduces the inflammatory response to Staphylococcus epidermidis (S. epidermidis) CNS catheter infection.MethodsIn this study, a murine model of catheter-associated S. epidermidis biofilm infection in the CNS was generated based on a well-established similar model for S. aureus. The catheters were pre-coated with a clinically derived biofilm-forming strain of S. epidermidis (strain 1457) which were then stereotactically implanted into the lateral left ventricle of 8-week-old C57BL/6 and IL-10 knockout (IL-10 knockout) mice. Bacterial titers as well as cytokine and chemokine levels were measured at days 3, 5, 7, and 10 in mice implanted with sterile and S. epidermidis-coated catheters.ResultsCultures demonstrated a catheter-associated and parenchymal infection that persisted through 10 days following infection. Cytokine analysis of the tissue surrounding the catheters revealed greater levels of IL-10, an anti-inflammatory cytokine, in the infected group compared to the sterile. In IL-10 KO mice, we noted no change in bacterial burdens, showing that IL-10 is not needed to control the infection in a CNS catheter infection model. However, IL-10 KO mice had increased levels of pro-inflammatory mediators in the tissues immediately adjacent to the infected catheter, as well as an increase in weight loss.ConclusionsTogether our results indicate that IL-10 plays a key role in regulating the inflammatory response to CNS catheter infection but not in control of bacterial burdens. Therefore, IL-10 may be a useful therapeutic target for immune modulation in CNS catheter infection but this should be used in conjunction with antibiotic therapy for bacterial eradication.
Highlights
Shunt infection is a frequent and serious complication in the surgical treatment in hydrocephalus
Very little has been studied about the role of IL-10 in response to S. epidermidis infection or biofilm infections but elevated levels of IL-10 have been associated with poor outcomes in patients with S. aureus bacteremia, suggesting this cytokine may play a role in staphylococcal disease [12]
Catheter-associated bacterial growth predominates during the initial post-implantation period, consistent with biofilm formation To assess the bacteriologic and inflammatory kinetics of S. epidermidis catheter-associated infection in the central nervous system (CNS), mice were implanted with silicone catheters precoated with S. epidermidis 1457
Summary
Shunt infection is a frequent and serious complication in the surgical treatment in hydrocephalus. Our laboratory developed a murine model of CNS catheter infection to generate a consistent catheterassociated infection with Staphylococcus aureus (S. aureus), mimicking what is seen in humans with ventricular shunt infections [7] Using this model, we have been able to demonstrate a relative decrease in inflammation in biofilm infections in the brain, as compared to abscess or infection with biofilm-deficient strains of bacteria [8]. Very little has been studied about the role of IL-10 in response to S. epidermidis infection or biofilm infections but elevated levels of IL-10 have been associated with poor outcomes in patients with S. aureus bacteremia, suggesting this cytokine may play a role in staphylococcal disease [12] In these studies, we have adapted our mouse model of S. aureus CNS catheter infection to generate infection with S. epidermidis and have used this model to define the contribution of IL-10 to the inflammatory response to CNS catheter infection. Our results show that alterations in IL-10 result in increases in inflammatory mediators and infiltration of peripheral immune cells but do not significantly impact bacterial burdens
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