Discussion - References.
Gram-negative bacteria, which are frequently detected in infected root canals and necrotic dental pulps, are responsible for inducing inflammation. Histological evidence has shown that pulp disease can be initiated long before bacterial cells reach the pulp tissue, suggesting that the inflammatory responses may be elicited from bacterial by-products rather than the bacteria (Sundqvist et al. 1989). LPS has been characterized as one such molecule that mediates a number of biological activities that can lead to the destruction of host tissues (Hirano et al.1988).
It has been reported that LPS could enhance the production of PGE2, IL-6, IL-8 and TNFa and stimulate IL-1b production by osteoblast-like cells (Keeting et al. 1991), gingival fibroblasts (Sismey-Durrant & Hopps 1991) and HDP cells (Haskill et al.1991).
It has been demonstrated that a more intensive IL-1 staining in inflamed pulps and significantly higher levels of IL-1 in the culture supernatant of tissues compared with healthy pulpal tissues (Dâ€™Souza et al.1989). Hosoya & Matsushima (1997), reported that P.e. LPS (Porphyromonas endodontailis, ATCC 35406) could stimulate IL-1b release from HDP cells in a time and dose-dependent manner to suggest that P.e. LPS can stimulate IL-1b production through enhancement of IL-1b gene expression and may be involved in the progression of inflammation in pulpal and periapical disease. These findings suggested that LPS has an important role in pulpal disease (Lertchirakarn et al. 1998).
FnLPS has also been isolated from infected and chronically inflamed radicular pulp may play an important role in pulpal and periapical diseases. In this study, we examined IL-1b release in HDP cells treated with FnLPS. The results showed that FnLPS stimulated IL-1b synthesis in a dose-dependent manner and could be blocked by IL-1ra. Addition of IL-1ra, 60 min after the pretreatment of FnLPS, still induced a decrease in IL-1b production. When added 90 min after FnLPS, no significant decrease was observed to suggest that IL- 1ra may prevent IL-1b from binding to the receptors, and the effect of the blockade may depend primarily on time of addition.
The chemical structure of IL-1ra is similar to IL-1b but it has a different biological activity. Blockade of IL-1 receptors with receptor antagonist in rabbits with Escherichia coli shock or colitis has been shown to reduce inflammatory responses (Dinarello 1994). Similarly, in the presence of the IL-1ra, there was reduced size of myocardial infarcts in dogs and a decrease in the severity and onset of arthritis in rats (Dinarello & Thompson 1991).
The efficacy of cytokines in various inflammatory diseases may include their ability to regulate the balance of agonist and antagonist. It was reported that the cytokine network played an important role in inflammation, and administration of IL-1ra to animals reduced the severity of inflammatory diseases. In the present study, strong staining was observed on neutrophils, plasmacytes, lymphocytes, vascular endothelial cells and fibroblasts in inflamed pulpal tissue, whilst only a few endothelial cells and macrophages were stained in normal pulpal tissues. The expression in different cells suggests that the recovery system need not be open in normal pulpal tissue, for the body has the ability of maintaining self-stabilization. The balance between the amount of IL-1 and IL-1ra may be critical in some diseases. A special example of this balance exists in the skin (Dinarello 1995). Skin keratinocytes contain large amounts of nonsecreted IL-1ra, for example, a form of IL-1ra is found in 10- to 100-fold higher concentrations in the keratinocytes. This intracellular IL-1ra may be serving as an anti-inflammatory agent buffering the inflammatory properties of IL-1 released from the skin, following injury. This study further supports the hypothesis that endogenous IL-1ra plays a role when the pulpal tissue is exposed to severe invasion. The results of the present study demonstrated that IL-1ra might down-regulate part of the IL-1activity and affect the severity of the inflammatory response.
The existence of a naturally occurring IL-1ra suggests that the body mounts its own response to inflammation and that synthesis of IL-1ra is a natural part of the resolution of the disease process. Endogenously produced IL-1 ra probably contributed to limiting the severity of disease, but might be inadequate in over whelming infection or acute inflammation. Providing exogenous IL-1ra in some of these situmations may have beneficial effects (Baergen et al.1994).
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