We examined the tissue response to subcutaneous injections of
particulate polymethylmethacrylate powder in fully immunocompetent C3Hf/Sed
mice as well as three strains of mice with different levels of lymphocyte
dysfunction. Five weeks after the injection, we found clearly demarcated
granulomas. Histological and immunohistochemical studies showed that these
granulomas were similar among all strains, with either paucity or absence
of lymphoid cells. In situ hybridization with use of complementary RNA
probes indicated that macrophages were synthesizing interleukin-1 beta
messenger RNA (mRNA), a marker of macrophage activation, and a cytokine
implicated in pathological bone resorption. We concluded that, in mice,
there is a lymphocyte-independent pathway of macrophage activation in
response to particulate polymethylmethacrylate. This suggests that the
foreign-body response to particulate orthopaedic biomaterials is
macrophage-initiated and maintained and that lymphocytes are not essential
to this response, although they may modulate it.