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

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 in terleukin-1, interleukin-6, tumor necrosis factor-alpha, and prostaglandin E2. In addition, other immunologic-agents, such as interferon-gamma, are pr esent in tissues harvested from the bone-implant interface of failed orthop edic implants. The present study examined the effects of interferon-gamma o n polymethylmethacrylate (PMMA) particle-challenged monocyte/macrophages in vitro. The effects of interferon-gamma were determined by measuring interl eukin-6 and tumor necrosis factor-alpha release by primary human monocyte/m acrophages following exposure to PMMA particles. Exposure of the monocyte/m acrophages to PMMA particles resulted in a dose-dependent release of interl eukin-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 th e presence of 1.0 and 10.0 ng/mL of interferon-gamma, respectively. Interfe ron-gamma challenge alone did not alter interleukin-6 release relative to c ontrols. In contrast to interleukin-6, interferon-gamma challenge stimulate d tumor necrosis factor-alpha release in a dose-dependent manner. In the pr esence of particles, addition of 1.0 and 10.0 ng/mL of interferon-gamma res ulted in 17% and 171% increases in the levels of tumor necrosis factor-alph a release, respectively, relative to cultures challenged solely with partic les. Blocking antibody to IFN-gamma inhibited the effect of IFN-gamma on pa rticle-induced interleukin-6 and tumor necrosis factor-alpha release. The d ata presented in this study demonstrate that the immunologic modulator inte rferon-gamma exacerbates monocyte/macrophage release of the pro-inflammator y cytokines interleukin-6 and tumor necrosis factor-alpha in response to PM MA particle challenge in vitro. (C) 1999 John Wiley & Sons.