CHICAGO, Illinois—Debris from metal joint implants triggers a cellular danger-warning pathway that fires up local inflammatory responses and sets the stage for early loosening and failure of the implant. This activation of the “inflammasome” explains how implant debris is sensed and transduced by macrophages into a proinflammatory response.
"The cells start screaming 'danger!'"—Nadim Hallab, MD
It was reported by Marco S. Caicedo, MD, and colleagues in the Journal of Orthopaedic Research.1 The researchers are at Rush University Medical Center in Chicago.

Circulating metal, screaming cells

Implant failure afflicts up to 10% of patients and is often caused by localized inflammation without infection. To examine this problem, the researchers studied macrophage responses to bits typical of metal-on-metal implants, including soluble cobalt, chromium, molybdenum, and nickel ions, and Co-Cr-Mo alloy particles. They found that such exposure activated the inflammasome pathway in macrophages. This pathway causes caspase-1-induced cleavage of intracellular pro-IL-1β to mature IL-1β, which then induced a broad proinflammatory response.

The authors write, “Our results demonstrate that these agents stimulate IL-1β secretion in human macrophages that is inflammasome mediated (i.e. NADPH-, caspase-1-, Nalp3-, and ASC-dependent). Thus, metal ion- and particle-induced activation of the inflammasome in human macrophages provides evidence of a novel pathway of implant debris-induced inflammation, where contact with implant debris is sensed and transduced by macrophages into a proinflammatory response.”

“As soon as joint replacement devices are implanted, they begin to corrode and wear away, releasing particles and ions that ultimately signal danger to the body's immune system,” said senior author Nadim Hallab, MD. Dr. Hallab said that when macrophages encounter the metallic debris, they “engulf it in sacs called lysosomes and try to get rid of the debris by digesting it with enzymes. But the particles damage the lysosomes,” Dr. Hallab said, “and the cells start screaming ‘danger!'”

Inflammasome might explain many types of joint implant failure

The researchers are currently extending these studies to research on inflammasome activation by polymeric and ceramic debris from non-metal implant devices.

The authors write, “If inflammasome activation can be elicited by all types of particulate implant debris, this pathway is likely important to patients with all types of articulating implants (including metal-on-polymer and ceramic-on-ceramic) and the general phenomenon of aseptic osteolysis.”

Reference
1. Caicedo MS, Desai R, McAllister K, et al. Soluble and particulate Co-Cr-Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: a novel mechanism for implant debris reactivity. Journal of Orthopaedic Research. 2009;1-8.