期刊
JOURNAL OF NEUROINFLAMMATION
卷 13, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s12974-016-0741-1
关键词
S. epidermidis; IL-10; Central nervous system; Cytokines; Chemokines; Biofilm; Catheter; Shunt
资金
- Fullbright-Cerrejon Scholarship
- Cheryl Ann Lozier Memorial Research Fund
- Edna Ittner Pediatric Research Support Fund
- National Institute of Neurologic Disorders and Stroke [1K08NS069812, 1R01NS092732]
- University of Nebraska Medical Center Department of Pediatrics
- University of Nebraska Medical Center Department of Pathology/Microbiology
Background: Shunt 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. Methods: In 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. Results: Cultures 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. Conclusions: Together 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.
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