title: IL-10 plays an important role in the control of inflammation but not in the bacterial burden in S. epidermidis CNS catheter infection.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
authors.forename: Yenis M
authors.initials: YM
authors.lastname: Gutierrez-Murgas
authors.affiliation: Department of Pediatrics, 985900 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA.
authors.forename: Gwenn
authors.initials: G
authors.lastname: Skar
authors.affiliation: Pediatric Residency Program, Baylor College of Medicine, San Antonio, TX, 78207, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Ramirez
authors.affiliation: Department of Pediatrics, 985900 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Beaver
authors.affiliation: Department of Pediatrics, 985900 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA. jsnowden@unmc.edu.|Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA. jsnowden@unmc.edu.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Snowden
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development; D001921:Brain / Q000378:metabolism / Q000382:microbiology; D002408:Catheters, Indwelling / Q000382:microbiology*; D004866:Equipment Contamination / Q000517:prevention & control; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D016753:Interleukin-10 / Q000172:deficiency / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000473:pathology; D013212:Staphylococcus epidermidis / Q000378:metabolism*
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10
keywords: Biofilm; Catheter; Central nervous system; Chemokines; Cytokines; IL-10; S. epidermidis; Shunt