Interleukin-10 inhibits cytokine synthesis in monocytes stimulated by titanium particles: evidence of an anti-inflammatory regulatory pathway.
The anti-inflammatory mediator interleukin-10 was investigated as a potential inhibitor of proinflammatory cytokine release in human peripheral blood monocytes activated with titanium particles. It inhibited the secretion of both tumor necrosis factor-alpha and interleukin-6 in a dose-dependent manner, with complete inhibition observed at 2 ng/ml. Co-culture experiments were performed to determine whether this cytokine may have functional importance as an inhibitor of the inflammatory response. When unstimulated lymphocytes and monocytes were co-cultured with titanium-stimulated monocytes, they significantly suppressed the secretion of both interleukin-6 and tumor necrosis factor-alpha. The inhibitory effect of these co-cultured cells could be partially blocked with the addition of an interleukin-10 neutralizing antibody. Interleukin-10 levels were measured in monocyte cultures treated with titanium particles as well as in fresh monocyte cultures treated with conditioned medium from titanium-stimulated monocytes. The latter experiments demonstrated marked stimulation of interleukin-10 secretion in conditioned medium-treated cultures, an effect that was related to the presence of tumor necrosis factor-alpha in the conditioned medium. The addition of titanium to conditioned medium-treated cultures markedly reduced the secretion of interleukin-10, suggesting that the most responsive cells are unstimulated monocytes exposed to agents released from activated monocytes. Altogether, the expression and responsiveness to interleukin-10 suggest a potential role for anti-inflammatory cytokines in regulation of the inflammatory response to wear debris.
Published In/Presented At
Pollice, P. F., Hsu, J., Hicks, D. G., Bukata, S., Rosier, R. N., Reynolds, P. R., Puzas, J. E., & O'Keefe, R. J. (1998). Interleukin-10 inhibits cytokine synthesis in monocytes stimulated by titanium particles: evidence of an anti-inflammatory regulatory pathway. Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 16(6), 697–704. https://doi.org/10.1002/jor.1100160611
Medicine and Health Sciences
Department of Surgery