INHIBITION OF THE TISSUE REACTION TO A BIODEGRADABLE BIOMATERIAL BY MONOCLONAL-ANTIBODIES TO IFN-GAMMA

Biomaterials are increasingly used for clinical applications. However, loss of function may occur owing to tissue reactions, which are mainl y caused by a variety of inflammatory reactions. Recently, we demonstr ated that macrophages (MO) and T cells play key roles in these reactio ns. Since immunological studies showed that the T cell-derived cytokin e interferon-gamma (IFN-gamma) activates MO, the aim of this study was to investigate the possibility of modulating tissue reactions to biod egradable biomaterials by inactivating IFN-gamma. Dermal sheep collage n (DSC) was used as a test biomaterial. DSC impregnated with anti-IFN- gamma or phosphate-buffered saline (control) was implanted in rats. Th e results showed that cellular ingrowth and formation and function of giant cells were strongly delayed by anti-IFN-gamma. Also, MHC class I I expression was strongly inhibited. In the treated DSC, some huge gia nt cells were formed at the interface but association with the DSC bun dles did not occur. Finally, in both the control and treated DSC, T ce lls and NK cells were rarely detected. This study demonstrates that IF N-gamma plays an important role in the inflammatory reaction to biomat erials. This reaction can be modulated by anti-IFN-gamma, which warran ts further studies of anti-IFN-gamma for clinical application to preve nt unwanted tissue reactions to biomaterials. (C) 1998 John Wiley & So ns, Inc.