IL-10 plays an important role in the control of inflammation but not in the bacterial burden in S. epidermidis CNS catheter infection

J Neuroinflammation. 2016 Oct 13;13(1):271. doi: 10.1186/s12974-016-0741-1.

Abstract

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.

Keywords: Biofilm; Catheter; Central nervous system; Chemokines; Cytokines; IL-10; S. epidermidis; Shunt.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biofilms / growth & development
  • Brain / metabolism
  • Brain / microbiology
  • Catheters, Indwelling / microbiology*
  • Equipment Contamination* / prevention & control
  • Inflammation / metabolism
  • Inflammation / microbiology
  • Interleukin-10 / deficiency
  • Interleukin-10 / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Staphylococcal Infections / metabolism*
  • Staphylococcal Infections / pathology
  • Staphylococcus epidermidis / metabolism*

Substances

  • IL10 protein, mouse
  • Interleukin-10