Interleukin-4 inhibits granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha expression by human monocytesin response to polymethylmethacrylate particle challenge in vitro

The outcome of total joint arthroplasty is determined by biological events at the bone-implant interface. Macrophages phagocytose implant or wear debr is at the interface and release proinflammatory mediators such as interleuk ins 1 and 6, tumor necrosis factor-alpha, and prostaglandin E-2 These media tors are thought to contribute to the resorption of periprosthetic bone. Pr evious studies of tissues harvested from the bone-implant interface of fail ed orthopaedic implants demonstrated a possible role for two other cytokine s, granulocyte-macrophage colony-stimulating factor and interleukin-4. The present study examined the effects of in vitro challenge with polymethylmet hacrylate p articles on the expression of granulocyte-macrophage colony-sti mulating factor by primary human monocytes/macrophages and the role of inte rleukin-4 in regulating this expression. The polymethylmethacrylate particl es caused a dose-dependent release of granulocyte macrophage colony-stimula ting factor at 48 hours. This release was accompanied by increased expressi on of interleukins 6 and 1beta and tumor necrosis factor-alpha. Release of the lysosomal enzyme hexosaminidase also increased in response to the parti cles. Interleukin-4, inhibited the expression of,granulocyte-macrophage col ony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha at 4 8 hours in a dose-dependent manner. The data presented in this study confir m the hypothesis that interleukin-4 downregulates particle-induced activati on of macrophages, as demonstrated by the decreased release of proinflammat ory mediators.