title: Comparison of the roles of IL-1, IL-6, and TNFalpha in cell culture and murine models of aseptic loosening.
abstract: Pro-inflammatory cytokines, such as IL-1, IL-6, and TNF, are considered to be major mediators of osteolysis and ultimately aseptic loosening. This study demonstrated that synergistic interactions among these cytokines are required for the in vitro stimulation of osteoclast differentiation by titanium particles. In contrast, genetic knock out of these cytokines or their receptors does not protect murine calvaria from osteolysis induced by titanium particles. Thus, the extent of osteolysis was not substantially altered in single knock out mice lacking either the IL-1 receptor or IL-6. Osteolysis also was not substantially altered in double knock out mice lacking both the IL-1 receptor and IL-6 or in double knock out mice lacking both TNF receptor-1 and TNF receptor-2. The differences between the in vivo and the cell culture results make it difficult to conclude whether the pro-inflammatory cytokines contribute to aseptic loosening. One alternative is that in vivo experiments are more physiological and that therefore the current results do not support a role for the pro-inflammatory cytokines in aseptic loosening. We however favor the alternative that, in this case, the cell culture experiments can be more informative. We favor this alternative because the role of the pro-inflammatory cytokines may be obscured in vivo by compensation by other cytokines or by the low signal to noise ratio found in measurements of particle-induced osteolysis.
authors.affiliation: Department of Orthopaedics, Case Western Reserve University and Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106-5000, USA.
authors.forename: Naoya
authors.initials: N
authors.lastname: Taki
authors.forename: Joscelyn M
authors.initials: JM
authors.lastname: Tatro
authors.forename: Robert
authors.initials: R
authors.lastname: Lowe
authors.forename: Victor M
authors.initials: VM
authors.lastname: Goldberg
authors.forename: Edward M
authors.initials: EM
authors.lastname: Greenfield
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001207:Asepsis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010014:Osteolysis / Q000139:chemically induced / Q000473:pathology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014025:Titanium / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D014025:Titanium