Interferon-gamma exacerbates polymethylmethacrylate particle-induced interleukin-6 release by human monocyte/macrophagesin vitro

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Abstract
Periprosthetic membranes commonly observed at sites of total joint implant loosening exhibit abundant macrophages and particulate debris. Macrophages phagocytose orthopedic debris and release the pro‐inflammatory mediators interleukin‐1, interleukin‐6, tumor necrosis factor‐alpha, and prostaglandin E2. In addition, other immunologic agents, such as interferon‐gamma, are present in tissues harvested from the bone–implant interface of failed orthopedic implants. The present study examined the effects of interferon‐gamma on polymethylmethacrylate (PMMA) particle‐challenged monocyte/macrophages in vitro. The effects of interferon‐gamma were determined by measuring interleukin‐6 and tumor necrosis factor‐alpha release by primary human monocyte/macrophages following exposure to PMMA particles. Exposure of the monocyte/macrophages to PMMA particles resulted in a dose‐dependent release of interleukin‐6 and tumor necrosis factor‐alpha at 48 h. The interleukin‐6 release in response to PMMA particle challenge was stimulated by 76% and 127% in the presence of 1.0 and 10.0 ng/mL of interferon‐gamma, respectively. Interferon‐gamma challenge alone did not alter interleukin‐6 release relative to controls. In contrast to interleukin‐6, interferon‐gamma challenge stimulated tumor necrosis factor‐alpha release in a dose‐dependent manner. In the presence of particles, addition of 1.0 and 10.0 ng/mL of interferon‐gamma resulted in 17% and 171% increases in the levels of tumor necrosis factor‐alpha release, respectively, relative to cultures challenged solely with particles. Blocking antibody to IFN‐gamma inhibited the effect of IFN‐gamma on particle‐induced interleukin‐6 and tumor necrosis factor‐alpha release. The data presented in this study demonstrate that the immunologic modulator interferon‐gamma exacerbates monocyte/macrophage release of the pro‐inflammatory cytokines interleukin‐6 and tumor necrosis factor‐alpha in response to PMMA particle challenge in vitro. © 1999 John Wiley & Sons, Inc. J Biomed Mater Res, 47, 1–7, 1999.