Interleukin-1 receptor type I gene-deficient mice are less susceptible to Staphylococcus epidermidis biomaterial-associated infection than are wild-type mice

Abstract

Elevated concentrations of interleukin-1 (IL-1) were found in tissue surrounding biomaterials infected with Staphylococcus epidermidis. To determine the role of IL-1 in biomaterial-associated 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(6) CFU of S. epidermidis or sterile saline. Neither mouse strain was susceptible to BAI around SE. IL-1R(-/-) mice with SEpvp implants had a no abscess formation and a reduced susceptibility to persistent S. epidermidis infection. The normal 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.

FIG. 1

(A) Frequency of subcutaneous abscesses along the inserted catheter segments in either wild-type mice of IL-1R^−/− mice. (B) Number of CFU of S. epidermidis RP62a cultured from the insertion site homogenates. (C) Number of adherent CFU of S. epidermidis RP62a cultured from subcutaneous implantation of SE and SEpvp after various periods of implantation and challenge with 10⁶ CFU of S. epidermidis RP62a. There were six mice per group per time point tested.

FIG. 2

Mean scores of infiltration, foreign-body giant cells, fibrosis, and encapsulation, four features characteristic for the implantation of a foreign body, at various time points after subcutaneous implantation of SE or SEpvp and challenge with 10⁶ CFU of S. epidermidis RP62a in either wild-type mice or IL-1R^−/− mice. There were six mice per group tested at each time point.

FIG. 3

Gross sections of subcutaneously implanted catheter segments in wild-type and IL-1R^−/− mice challenged with S. epidermidis stained with hematoxylineosin. $, abscess formation; #, giant-cell formation; ∗, thickness of the capsule; arrows, catheter-tissue interface.

FIG. 4

Mean (± standard error) implantation site concentrations of IL-1β, IL-1α, and IL-4 at 2, 5, and 14 days after subcutaneous implantation of SE or SEpvp in wild-type of IL-1R^−/− mice challenged with 10⁶ CFU S. epidermidis RP62a. There were six mice per group tested at each time point. ∗, P < 0.05 by ANOVA, ⇒, P < 0.05 for over-time levels by general linear model-ANOVA.