ROLE FOR INTERLEUKIN-4 IN FOREIGN-BODY GIANT-CELL FORMATION ON A POLY(ETHERURETHANE UREA) IN-VIVO

Interleukin-4 (IL-4) was previously shown to induce extensive macropha ge fusion to form foreign-body giant cells (FBGCs) in vitro. In the pr esent study, our goal was to extend these findings to an in vivo test environment on biomaterials. The subcutaneous cage-implant system was modified for mice to elucidate IL-4 participation in mediating FBGC fo rmation in vivo. Exudate leukocyte concentrations from cages containin g poly(etherurethane urea) (PEUU A') and empty cage controls indicated a similar inflammatory response that turned toward resolution by 14 d ays postimplantation, thus confirming the applicability of the cage-im plant system in mice. FBGC kinetic analysis showed that the formation of mouse FBGCs occurs through the fusion of adherent macrophages at a constant rate up to 14 days of implantation. Purified goat anti-mouse IL-4 neutralizing antibody (IL4Ab) or normal goat nonspecific control IgG (gtIgG) at various concentrations, or recombinant murine IL-4 (muI L4) was injected into the implanted cages containing PEUU A' every 2 d ays for 7 days. The injection of IL4Ab significantly decreased the FBG C density on PEUU A' cage-implanted in mice, when compared with the no nspecific IgG or PBS injection controls. Conversely, the FBGC density was significantly increased by the injection of muIL4 when compared wi th nonspecific IgG and PBS injection controls. Adherent macrophage den sity, FBGC morphology, FBGC average size, and size distribution were n ot significantly different among IL4Ab, nonspecific control gtIgG, muI L4, and PBS control groups. Our data suggest that IL-4 participates in FBGC formation on biomaterials in vivo. (C) 1995 John Wiley & Sons, I nc.