Elevated concentrations of interleukin (IL)-l were found in tissue surrounding biomaterials infected with Staphylococcus epidermidis. To determine the role of IL-1 in biomaterialassociated infection (BAI), IL-1 receptor type I deficient (IL-1R-/-) and wild-type mice received subcutaneous implants of silicon elastomer (SE) or polyvinylpyrrolidone-grafted SE (SEpvp), combined with an injection of 10 cfu S. epidermidis or sterile saline. Neither mouse strain was susceptible to BAI around SE. IL-1R-/mice had a no abscess formation and a reduced susceptibility to persistent S. epidermidis-infection associated with SEpvp. The foreign body response, characterized by giant-cell formation and encapsulation, was delayed around SEpvp in wild-type mice but not in IL-1R-/mice. This coincided with enhanced local IL-4 production in IL-1R-/mice. These data suggest that inhibition of local IL-1 activity may be beneficial for the outcome of BAI.

ABSTRACT Biomaterial-associated infections (BAI), which are predominantly caused by Staphylococcus epidermidis , are a significant problem in modern medicine. Biofilm formation is considered the pivotal element in the pathogenesis, but in previous mouse studies we retrieved S. epidermidis from peri-implant tissue. To assess the kinetics and generality of tissue colonization, we investigated BAI using two S. epidermidis strains, two biomaterials, and two mouse strains. With small inocula all implants were culture negative, whereas surrounding tissues were positive. When higher doses were used, tissues were culture positive more often than implants, with higher numbers of CFU. This was true for the different biomaterials tested, for both S. epidermidis strains, at different times, and for both mouse strains. S. epidermidis colocalized with host cells at a distance that was >10 cell layers from the biomaterial-tissue interface. We concluded that in mouse experimental BAI S. epidermidis peri-implant tissue colonization is more important than biofilm formation.

Biomaterial surfaces may be modified to reduce bacterial adhesion. The susceptibility in mice to Staphylococcus epidermidis infection in tissue surrounding the commonly used catheter materials-silicon elastomer (SE), polyamide (PA), and their surface-modified polyvinylpyrrolidone (PVP)-grafted derivatives, SE-PVP and PA-PVP, respectively-was assessed. Abscesses developed around SE-PVP. Around SE, PA, and PA-PVP catheters, no signs of infection were observed, although mice carrying PA-PVP developed septicemia after 14-21 days. S. epidermidis was cultured from the tissue surrounding PA-PVP segments. Cells around PA-PVP segments containing large numbers of bacteria were identified as macrophages by use of immunohistochemistry and electron microscopy. This persistence of intracellular bacteria was also observed around SE-PVP, SE, and PA catheters, although to a lesser extent. The cytokine profiles around the 4 materials were different. Implanted biomaterial induces an inflammatory response favorable to the persistence of S. epidermidis. Intracellular persistence of bacteria inside macrophages may be a pivotal process in the pathogenesis of biomaterial-associated infection.

ABSTRACTA persistentStaphylococcus epidermidisinfection in mice around a subcutaneous polyvinylpyrrolidone-grafted silicon elastomer catheter (SEpvp) but not around a conventional silicon elastomer catheter was observed. With SEpvp pericatheter tissue, protracted and exaggerated interleukin-1β (IL-1β) production was found. Apparently, sustained levels of IL-1β are associated with enhanced susceptibility to biomaterial-associatedS. epidermidisinfection.