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 pro‐inflammatory 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.