Objective: Interleukin-1a and IL-1b are implicated in inflammatory bone destruction in pulpal infections; however, their protective effects are less well understood. In these studies an antibody neutralization strategy was used to investigate the role of IL-1 isoforms in resistance to pulpal infections. Methods: C57Bl/6 mice were subjected to molar pulp exposure and infection with 4 endodontic pathogens (P. micros, P. intermedia, F. nucleatum, S. intermedius). In Expts. 1 and 2, four groups of animals (males = females) were assessed: Group 1: no treatment; Group 2; neutralizing anti-IL-1a antibody (Ab); Group 3: anti-IL-1b Ab; Group 4: anti-IL-1a + anti-IL-1b Ab (IL-1a/b). The effect of Ab treatment on infection dissemination (abscess formation), body weight, splenomegaly, and periapical inflammatory cells were evaluated. IL-1a, IL-1b, TNFa, IL-6, IL-10, IFNg were measured by ELISA. In Expt. 3, the effect of estrogen was assessed in females (n=11/group): Group 1: sham; Group 2: sham + anti-IL-1 a/b; Group 3: ovariectomy (ovx); Group 4: ovx + anti-IL-1a/b; Group 5: ovx + estrogen supplementation (E2); group 6: ovx + anti-IL-1a/b + E2. The ex vivo phagocytosis and killing of F. nucleatum by blood leukocytes was also determined. Results: In Expts. 1 and 2, only male mice that received anti-IL-1a/b developed severe orofacial abscesses (p<0.05). Inflammatory cells were elevated in these lesions, suggesting ineffective bacterial killing, and there was a reduction in IFNg. In Expt. 3, 70% of mice receiving ovx + anti-IL-1a/b (Group 4) developed abscesses vs. 12% in all other groups combined (p<0.01). Group 4 also had significantly reduced body weight, splenomegaly, and reduced ex vivo phagocytic and killing ability of leukocytes. Conclusions: IL-1a and IL-1b enhance leukocyte phagocytosis and bacteriocidal activity, and prevent disseminating orofacial infections and sepsis in estrogen-deficient animals. Males may therefore be at increased risk for developing severe orofacial infections. Supported by N.I.D.C.R. DE-11664.

Back to the AADR/Pfizer Hatton Awards Program
Back to the IADR/AADR/CADR 82nd General Session (March 10-13, 2004)

Top Level Search