Azithromycin suppresses P. gingivalis LPS-induced pro-inflammatory cytokine and chemokine production by human gingival fibroblasts in vitro.

OBJECTIVE: Azithromycin is a macrolide antibiotic that appears to have both antibacterial and anti-inflammatory properties. This study aimed to investigate the effect of azithromycin on the production of pro-inflammatory cytokines and chemokines by human gingival fibroblasts (HGF) in vitro. MATERIALS AND METHODS: The effects of azithromycin (0.1 to 10 µg/mL) on the production of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), and growth-regulated oncogene (GRO) by human gingival fibroblasts cultured in the presence or absence of Porphyromonas gingivalis lipopolysaccharide (LPS) was studied. Cytokine and chemokine protein levels in the culture supernatant were assessed using a Luminex® multiplex immunoassay. RESULTS: P. gingivalis LPS induced cytokine/chemokine (IL-6, IL-8, MCP-1, and GRO) protein production in HGFs, and this effect was suppressed by azithromycin at all concentrations tested. CONCLUSIONS: This study demonstrates that azithromycin suppresses P. gingivalis LPS-induced cytokine/chemokine protein production in HGF, which may explain some of the clinical benefits observed with the adjunctive use of azithromycin in the treatment of periodontitis. CLINICAL RELEVANCE: The current study examines the anti-inflammatory properties of azithromycin which may make it useful as an adjunct treatment to periodontitis. Specifically, we used azithromycin to modulate the production of pro-inflammatory cytokines by gingival fibroblasts known to be important in periodontal inflammation.

Expression of peptidylarginine deiminase-2 and -4, citrullinated proteins and anti-citrullinated protein antibodies in human gingiva.

BACKGROUND AND OBJECTIVE: The presence of citrullinated proteins, and peptidylarginine deiminase types -2 (PAD-2) and -4 (PAD-4) in periodontal tissues, determine the presence of anti-cyclic citrullinated protein antibodies (anti-CCP) in gingival crevicular fluid (GCF) and compare the expression of these proteins between inflamed and non-inflamed sites. MATERIAL AND METHODS: Tissue sections were stained using antibodies against citrullinated proteins, PAD-2 and PAD-4. RT-PCR was performed to investigate PAD-2 and PAD-4 mRNA in inflamed and non-inflamed gingival tissues. Anti-CCP antibodies in gingival crevicular fluid were detected by ELISA. RESULTS: Citrullinated proteins, PAD-2 and PAD-4 were detected in gingiva. There was a correlation between inflammation and expression of these proteins. mRNAs for PAD-2 and PAD-4 were detected in both inflamed and non-inflamed gingival tissues. Antibodies to CCP were found mostly in the GCF of individuals with periodontitis. CONCLUSION: PAD-2 and PAD-4 (protein and mRNA) as well as citrullinated proteins are present in inflamed gingiva, and anti-CCP antibodies can be detected in the GCF of some patients. Tissue expression of citrullinated proteins and PAD increased with the severity of inflammation. The presence of anti-CCP antibodies in GCF was almost exclusive to a subset of patients with periodontitis. Increased expression of these proteins in inflamed gingiva lends support to the notion that periodontal inflammation contributes to the inflammatory burden in a similar way to rheumatoid arthritis.

Biomarkers of periodontal inflammation in the Australian adult population.

BACKGROUND: Several inflammatory biomarkers are implicated in the pathogenesis of periodontitis including interleukin-1beta (IL-1beta) and C-reactive protein (CRP). This study investigated the presence of these factors in gingival crevicular fluid (GCF) and their relationship to clinical and social determinants of periodontitis in the Australian population. METHODS: Equal numbers of periodontitis cases and non-cases were sampled during oral epidemiologic examination in the National Survey of Adult Oral Health. GCF was sampled from four sites where probing pocket depth (PPD) and recession were recorded. From these, IL-1beta and CRP were quantified by ELISA and the log amount of GCF IL-1beta (pg) per person and the proportion of adults with detectable CRP was computed. RESULTS: Periodontitis cases (n = 511) had significantly higher levels of IL-1beta and CRP than non-cases (n = 562). PPD, clinical attachment loss, plaque and gingivitis indices were positively associated with elevated levels of both biomarkers. Levels of both were positively associated with age, low socio-economic position and non-Australian birth. CONCLUSIONS: The presence of IL-1beta and CRP in GCF are associated with periodontal disease parameters within the Australian population. The levels of both biomarkers are influenced by age, education and eligibility for public dental care.

Diagnosis and management of the autonomously functioning thyroid nodule: the Walter Reed Army Medical Center experience, 1975-1996.

In order to characterize the clinical and laboratory features of autonomously functioning thyroid nodules (AFTNs), and to assess optimal diagnosis and management of patients with this disorder, we performed a retrospective analysis of 49 such patients over a 22-year period encompassing January 1975 to November 1996. The following data were analyzed: thyroid hormone levels, thyroid scintiscan, radioiodine uptake, fine-needle aspiration biopsy, triiodothyronine (T3) suppression testing, thyrotropin-releasing hormone (TRH) stimulation test, and thyroid ultrasound. Clinical outcomes assessed included persistent hyperthyroidism, hypothyroidism, and nodule shrinkage after treatment, or in patients followed without definitive therapy, nodule growth, spontaneous degeneration, and progression to hyperthyroidism. Biochemical hyperthyroidism, often subclinical, was found in 73.5% of patients at presentation and in an additional 24.4% of patients during subsequent follow-up. The introduction of sensitive thyrotropin (TSH) testing during the period of study resulted in a decrease in the use of the T3-suppression test and TRH stimulation test from 100% and 20%, respectively, in the period from 1976-1980, to 4% each in the period from 1991-1996. T3-thyrotoxicosis occurred in 12.2% of patients. Thyrotoxicosis at any time during the course of follow-up was positively correlated with nodule size at diagnosis. Definitive therapy, used in 42.8% of patients, consisted of radioiodine ablation (38.1%) or thyroidectomy (61.9%). No patient had recurrence of thyrotoxicosis after definitive therapy, but 25% became hypothyroid. During follow-up for a mean of 30.9 months, nodules enlarged in 25% of patients overall, or 33% of patients not receiving definitive therapy. Cystic degeneration was documented in 26.5% of patients, although this change rarely reversed subclinical hyperthyroidism. The diagnosis of an AFTN requires a demonstration of TSH-independent nodular hyperfunction. The introduction of sensitive TSH assays has simplified the evaluation of AFTN patients and revealed a high prevalence of subclinical thyroid hyperfunction in this disorder. In view of current increased awareness of adverse consequences associated with subclinical hyperthyroidism and the rarity of spontaneous resolution of hyperthyroidism in AFTN patients (despite a propensity for spontaneous hemorrhage), definitive therapy is recommended. Both radioiodine and hemithyroidectomy have high cure rates and a low posttreatment incidence of hypothyroidism.