title: Interleukin-10 inhibits cytokine synthesis in monocytes stimulated by titanium particles: evidence of an anti-inflammatory regulatory pathway.
abstract: 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.
authors.affiliation: Department of Orthopaedics, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Pollice
authors.forename: J
authors.initials: J
authors.lastname: Hsu
authors.forename: D G
authors.initials: DG
authors.lastname: Hicks
authors.forename: S
authors.initials: S
authors.lastname: Bukata
authors.forename: R N
authors.initials: RN
authors.lastname: Rosier
authors.forename: P R
authors.initials: PR
authors.lastname: Reynolds
authors.forename: J E
authors.initials: JE
authors.lastname: Puzas
authors.forename: R J
authors.initials: RJ
authors.lastname: O'Keefe
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D016753:Interleukin-10 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008214:Lymphocytes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D014025:Titanium / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014025:Titanium