TISSUE-RESPONSE TO PARTICULATE POLYMETHYLMETHACRYLATE IN MICE WITH VARIOUS IMMUNE DEFICIENCIES

We examined the tissue response to subcutaneous injections of particul ate polymethylmethacrylate powder in fully immunocompetent C3Hf/Sed mi ce as well as three strains of mice with different levels of lymphocyt e dysfunction. Five weeks after the injection, we found clearly demarc ated granulomas. Histological and immunohistochemical studies showed t hat these granulomas were similar among all strains, with either pauci ty or absence of lymphoid cells, In situ hybridization with use of com plementary RNA probes indicated that macrophages were synthesizing int erleukin-1 beta messenger RNA (mRNA), a marker of macrophage activatio n, and a cytokine implicated in pathological bone resorption. We concl uded that, in mice, there is a lymphocyte-independent pathway of macro phage activation in response to particulate polymethylmethacrylate, Th is suggests that the foreign-body response to particulate orthopaedic biomaterials is macrophage-initiated and maintained and that lymphocyt es are not essential to this response, although they may modulate it. CLINICAL RELEVANCE: The mammalian response to particulate biomaterials does not appear to fit a specific immune hypersensitivity response; r ather, it seems to follow a non-specific pattern of macrophage phagocy tosis, activation, and cellular response to monokine release, Differen ces in the response to debris among patients, manifested by difference s in the rapidity and extent of osteolysis around joint prostheses, ar e more probably related to factors other than the hypersensitivity res ponse, such as the amount of particles released, individual difference s in macrophage activation, or intracellular damage created by the par ticles after phagocytosis.