The interleukin-10 knockout mouse is highly susceptible to Porphyromonas gingivalis-induced alveolar bone loss.
OBJECTIVE
Interleukin-10 is an anti-inflammatory cytokine that reduces periapical bone loss, but its role in periodontal bone loss is unclear. In the present study, we tested the hypothesis that endogenous interleukin-10 is a potent suppressor of Porphyromonas gingivalis-induced alveolar bone loss in vivo.


METHODS
Interleukin-10 knockout (-/-) and wild-type mice were inoculated intraorally with P. gingivalis. Non-infected animals served as negative controls. Alveolar bone loss, gingival cytokine levels, and gingival gene expression were assessed using morphometric analysis, enzyme-linked immunosorbent assay (ELISA), and semiquantitative reverse transcription polymerase chain reaction (RT-PCR), respectively.


RESULTS
P. gingivalis-infected interleukin-10(-/-) mice exhibited severe alveolar bone loss compared to non-infected interleukin-10(-/-) and wild-type mice by day 42. Surprisingly, bone resorptive cytokines interleukin-1alpha and tumor necrosis factor alpha (TNF-alpha) were not up-regulated in gingival tissues by P. gingivalis-infection. Although interleukin-1beta was marginally increased, blockade of both interleukin-1 isoforms or interleukin-1 receptor type I with neutralizing antisera failed to reduce alveolar bone loss in interleukin-10(-/-) mice, indicating the operation of an interleukin-1-independent mechanism. No strong correlations between bone loss and other cytokines was observed, although interferon gamma (IFNgamma), interleukin-6, interleukin-4, and prostaglandin E2 were modestly up-regulated in infected interleukin-10(-/-) mice. P. gingivalis infection reduced the expression of cell markers in gingival tissue on days 7 and 14 in both interleukin-10(-/-) and wild-type animals, suggestive of bacteria-induced cytotoxicity or apoptosis. This was followed by up-regulated expression of receptor activator of nuclear factor kappa B ligand (RANKL) and CD40 ligand (CD40L on days 28 and 70 in infected interleukin-10(-/-) mice only.


CONCLUSIONS
The interleukin-10(-/-) mouse is highly susceptible to bone loss induced by the periodontal pathogen P. gingivalis, which is mediated via an interleukin-1-independent pathway.
Sasaki
Hajime
H
Department of Cytokine Biology, The Forsyth Institute, Boston, MA 02115, USA.
Okamatsu
Yoshimasa
Y
Kawai
Toshihisa
T
Kent
Ralph
R
Taubman
Martin
M
Stashenko
Philip
P
D016301:Alveolar Bone Loss / Q000382:microbiology*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D019013:CD40 Antigens / Q000096:biosynthesis; D002352:Carrier Proteins / Q000096:biosynthesis; D004195:Disease Models, Animal; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation
D019013:CD40 Antigens; D002352:Carrier Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D016753:Interleukin-10