Related Experiment Video
Updated: Aug 9, 2026
Assessment of Antibody-based Drugs Effects on Murine Bone Marrow and Peritoneal Macrophage Activation
Published on: December 26, 2017
Interferon-gamma exacerbates polymethylmethacrylate particle-induced interleukin-6 release by human
M C Trindade1, M Lind, S B Goodman
1Orthopaedic Research Laboratory, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305-5341, USA.
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.
Insights
Interferon-gamma amplifies the release of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha from macrophages exposed to orthopedic debris. This finding is crucial for understanding implant loosening and inflammation.
Area of Science:
- Biomedical Engineering
- Immunology
- Materials Science
Background:
- Periprosthetic membranes at failed joint implants contain macrophages and debris.
- Macrophages release pro-inflammatory mediators like interleukin-6 and tumor necrosis factor-alpha.
- Interferon-gamma is present at the bone-implant interface of failed orthopedic implants.
Purpose of the Study:
- To investigate the in vitro effects of interferon-gamma on monocyte/macrophages challenged with polymethylmethacrylate (PMMA) particles.
- To quantify the release of interleukin-6 and tumor necrosis factor-alpha under these conditions.
Main Methods:
- Primary human monocyte/macrophages were exposed to PMMA particles.
- Interferon-gamma was added at varying concentrations (1.0 and 10.0 ng/mL).
- Interleukin-6 and tumor necrosis factor-alpha release was measured; blocking antibodies to interferon-gamma were used.
Main Results:
- PMMA particles induced a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha.
- Interferon-gamma significantly increased interleukin-6 release (76-127%) and tumor necrosis factor-alpha release (17-171%) in response to PMMA particles.
- Interferon-gamma alone did not affect interleukin-6 release, but stimulated tumor necrosis factor-alpha release.
Conclusions:
- Interferon-gamma exacerbates the release of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha from macrophages stimulated by PMMA particles.
- This suggests interferon-gamma plays a role in the inflammatory response associated with orthopedic implant debris.
- Findings highlight interferon-gamma as a potential target for managing implant-associated inflammation.
