Secretion of IL‐1β, TNF‐α, IL‐8 and IL‐1ra by human polymorphonuclear leukocytes in response to lipopolysaccharides from periodontopathic bacteria

Abstract

Polymorphonuclear leukocytes (PMN) are the first cells that migrate into periodontal tissues and gingival crevices in response to invading pathogens. It was recently demonstrated that PMN have the ability to synthesize and release cytokines following appropriate stimulation, while it is not clear whether these capacities are directly related to periodontal destructive processes. We therefore investigated the amounts of the cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), IL-8 and IL-1 receptor antagonist (IL-1ra) secreted by PMN from healthy donors following stimulation with lipopolysaccharide (LPS) from 4 periodontopathic bacteria, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Capnocytophaga ochracea and Fusobacterium nucleatum, and the non-oral bacterium Escherichia coli. A actinomycetemcomitans, F. nucleatum and E. coli LPS stimulated the release of significantly greater amounts of IL-1 beta, TNF-alpha and IL-8 than the control unstimulated PMN (p < 0.01). The levels of IL-1 beta, TNF-alpha and IL-8 released from cells stimulated with P. gingivalis or C. ochracea LPS were significantly lower than those of cells stimulated with A. actinomycetemcomitans or E. coli LPS (p < 0.05). On the other hand, substantially greater amounts of IL-1ra were released from PMN stimulated with each LPS and from control unstimulated PMN during the first 6 h, and then significantly greater amounts of IL-1ra were secreted by PMN stimulated with A. actinomycetemcomitans and E.coli LPS during the following 12 h (p < 0.01). The inhibitory effects of IL-1ra on the biological activity of IL-1 in the supernatants of PMN were examined by the thymocyte comitogen proliferation assay. The supernatants of PMN stimulated with each LPS showed less biological IL-1 activity as compared with the same doses of recombinant human IL-1 beta detected by enzyme-linked immunosorbent assay. Furthermore, no activity was detected in the supernatants of PMN stimulated with P. gingivalis or C. ochracea LPS. These findings demonstrated that LPS from periodontopathic bacteria were capable of stimulating PMN to release not only pro-inflammatory cytokines but also their inhibitors such as IL-1ra. Different secretion levels of these cytokines and their biological activities induced by the various LPS might be important in the onset and progression of periodontal diseases.

The role of macrophages in the induction of murine immune response to Actinobacillus actinomycetemcomitans

“…Evidence has shown that the numbers of this micro-organism are increased in patients with periodontal disease, especially those with early-onset periodontitis [3][4][5][6]. Human monocytes and polymorphonuclear neutrophils stimulated with this potential periodontopathogen have been shown to release proinflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor (TNF-AE) [7,8]. A. actinomycetemcomitans has been shown to induce alveolar bone destruction in animal models [9].…”

Bacterial pathogenesis and mediators in apical periodontitis

“…Thus, which factors are involved in each specific case will depend on the composition of the microbiota, i.e., the bacterial species present in the necrotic root canal. It is still worth pointing out that the potency of biological effects of the same virulence factor (e.g., LPS) can significantly vary from species to species (92,93). Thus, given the nonspecific nature of primary endodontic infections, different combinations of virulence factors will cause disease in different subjects.…”

Minocycline hydrochloride nanoliposomes inhibit the production of TNF-&alpha; in LPS-stimulated macrophages

“…TNF-α originates mainly from activated macrophages release; it is expressed in higher levels in the gingival crevicular fluid and inflamed periodontium of patients with clinical periodontium disease than in healthy people, and it also causes alveolar bone resorption. 22 As a conventional anti-inflammatory agent, minocycline hydrochloride exerts anti-inflammatory activity in macrophages and other immune cells, and these effects were independent of its antimicrobial action. It had been demonstrated having a long-term reductive effect on subgingival microorganisms, which was one of its main purposes in the course of periodontitis treatment.…”