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ABSTRACT
Vascular disruption and bleeding during periodontitis likely increase the levels of hemoglobin in gingival crevicular fluid. The aim of this study was to investigate the effect of hemoglobin on the inflammatory responses of human macrophages stimulated with lipopolysaccharides (LPS) isolated from periodontopathogens. The production of interleukin-1 beta (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) by macrophages following challenges with Porphyromonas gingivalis and Fusobacterium nucleatum LPS in the presence or absence of human hemoglobin was analyzed by ELISA. The effect of hemoglobin on LPS-binding to macrophages was evaluated with ^sup 3^H-LPS. Hemoglobin and LPS from periodontopathogens acted in synergy to stimulate the production of high levels of IL-1β, IL-6, IL-8, and TNF-α by macrophages. Hemoglobin also enhanced LPS-binding to macrophages. This study suggests that hemoglobin contributes to increases in the levels of pro-inflammatory mediators in periodontal sites by acting in synergy with LPS from periodontopathogens, thus favoring the progression of periodontitis.
KEY WORDS: cytokine, Fusobacterium nucleatum, periodontitis, Porphyromonas gingivalis.
INTRODUCTION
Periodontitis is a multifactorial polymicrobial infection characterized by a destructive inflammatory process resulting in the loss of tooth-supporting tissues. Porphyromonas gingivalis and Fusobacterium nucleatum are major periodontopathogens (Moore and Moore, 1994), and their numbers in subgingival plaque increase significantly during the active phase of periodontitis (van Winkelhoff et al, 2002). The host response to these bacterial species and their products, such as lipopolysaccharides (LPS), is a critical determinant in the initiation and progression of periodontitis (Agarwal et al, 1995; Wilson, 1995). Excessive, continuous production of cytokines - including interleukin (IL)- Iß, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) - in inflamed periodontal tissues is responsible for disease progression and periodontal tissue destruction (Okada and Murakami, 1998).
The periodontal tissue of persons affected with periodontitis is highly infiltrated with macrophages that play an essential role in the host response to periodontopathogens (Okada and Murakami, 1998). A clinical characteristic of periodontitis is vascular disruption and bleeding. Hemoglobin accounts for 95% of the protein content of erythrocytes and is present in both plasma and gingival crevicular fluid. Several studies have revealed a close relationship between bleeding on probing and inflamed gingival tissue (Abrams et al, 1984; Thilo et al, 1986). A correlation between hemoglobin concentration in gingival tissue and the active phase of...