Interleukin-10 inhibits polymethylmethacrylate particle induced interleukin-6 and tumor necrosis factor-alpha 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 E-2. Populations of activated lymphocytes are often seen in periprosthetic membranes. These lymphocytes may modulate the monocyte/macrophage response to particulate debris and influence aseptic loosening. In addition, other i mmunologic agents, such as interleukin-10, are present in tissues harvested from the bone-implant interface of failed total joint arthroplasties. The present study examined the effects of interleukin-10 on polymethylmethacryl ate (PMMA) particle challenged human monocyte/macrophages. in vitro. Human monocyte/macrophages isolated from buffy coats of five healthy individuals were exposed to 1-10 mum PMMA particles. Interleukin-10 was added to the mo nocyte/macrophage with and without the addition of PMMA particles. Interleu kin-10-induced alterations in monocyte/macrophage metabolism were determine d measuring interleukin-6 and tumor necrosis factor-alpha release by the ce lls following exposure to PMMA particles. Exposure of the monocyte/macropha ges to PMMA particles resulted in a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha at 48 h. Interleukin-10 reduced the levels of interleukin-6 and tumor necrosis factor-alpha release by macrophages in response to PMMA particles in a dose-dependent manner. At 48 h, particle-i nduced interleukin-6 release was inhibited by 60 and 90% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. At 48 h, particle-induced tumor necrosis factor-x release was inhibited by 58 and 88% with 1.0 and 1 0.0 ng/ml treatments of interleukin-10, respectively. Interleukin-10 challe nge alone did not significantly alter basal interleukin-6 or tumor necrosis factor-alpha release relative to control cultures. The data presented in t his study demonstrate that the anti-inflammatory cytokine, interleukin-10, inhibits monocyte/macrophage release of the pro-inflammatory cytokines inte rleukin-6 and tumor necrosis factor-a in response to PMMA particle challeng e in vitro. (C) 2001 Elsevier Science Ltd. All rights reserved.