RESUMO
Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that is thought to play a role in the pathogenesis of periodontal disease. TNF-alpha production is regulated by many factors, including certain alleles of TNF gene polymorphisms. In the present study, TNF genotypes of 3 bi-allelic polymorphisms were determined in 32 Caucasian patients with adult periodontitis and 32 orally-healthy matched controls, and correlated with TNF-alpha production by oral polymorphonuclear leukocytes (PMN). No differences in distribution of TNF alleles of the -238, -308, or +252 gene polymorphisms were observed between patients and controls or between patients with different disease severity. However, the level of TNF-alpha production by oral PMN correlated with the TNF-alpha 308 genotype in patients with adult periodontitis, with increased production found in patients with the T1,2 genotype (t-test; P=0.037). When cytokine production was examined in patients according to disease severity, an association between the T1,2 genotype and increased production was observed only in patients with advanced disease (t-test; P=0.05). These findings suggest that further studies are warranted to determine if the TNF genotype is a risk factor for severity of disease in adult periodontitis.
Assuntos
Neutrófilos/metabolismo , Periodontite/genética , Periodontite/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Índice de Gravidade de DoençaRESUMO
Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) also possess bone-resorptive properties, and are generally considered to play a role in the pathogenesis of periodontal disease. In the present study, TNF-alpha and IL-1 beta production by oral and peripheral blood polymorphonuclear leukocytes (PMN) was examined in 40 patients with adult periodontitis and 40 orally healthy matched controls. Oral PMN released considerable amounts of both cytokines in unstimulated culture, and there was no difference between patients and controls when the cytokine levels were corrected for cell number. However, when the effect of disease activity was examined, cytokine release by oral PMN was found to be greatest in patients with advanced periodontitis. Within the healthy control group, IL-1 beta production by oral PMN was significantly higher in males (Mann-Whitney test, P = 0.0008). Examination of IL-1 beta production by peripheral blood PMN exposed to recombinant human granulocyte-macrophage colony stimulating factor revealed no difference between the patient and control groups. In contrast, IL-1 beta production by peripheral blood PMN was significantly reduced in patients with advanced disease (Mann-Whitney test, P = 0.02), and peripheral PMN IL-1 beta synthesis was greater in female controls (Mann-Whitney test, P = 0.054). No effect of race on cytokine production could be discerned in patients or controls. These results indicate that several factors influence cytokine production in oral health and disease, and that a dichotomy in cytokine gene expression exists between oral and peripheral blood PMN in adult periodontitis.
Assuntos
Interleucina-1/biossíntese , Mucosa Bucal/imunologia , Neutrófilos/imunologia , Periodontite/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Adulto , População Negra , Reabsorção Óssea/imunologia , Estudos de Casos e Controles , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Interleucina-1/genética , Contagem de Leucócitos , Masculino , Mucosa Bucal/patologia , Neutrófilos/patologia , Periodontite/etiologia , Periodontite/patologia , RNA Mensageiro/análise , RNA Mensageiro/genética , Proteínas Recombinantes , Fatores Sexuais , Fator de Necrose Tumoral alfa/genética , População BrancaRESUMO
Oral polymorphonuclear leukocytes (PMN) were obtained from 10 adult donors in good oral health using a method employing repeated mouth rinse collection. Interleukin-1 beta (IL-1 beta) mRNA was detected in freshly obtained cells by blot hybridization of total cellular RNA with a biotin labeled cDNA probe. Supernates from oral PMN placed in culture for 3 hours contained substantial amounts of IL-1 beta measured by ELISA. Significantly greater numbers of PMN and amounts of PMN-derived IL-1 beta were obtained from the same donors 2 hours subsequent to an oral sucrose challenge (3.23 x 10(6) vs. 1.57 x 10(6) mean PMN number, P = 0.004; 59.80 vs. 20.05 mean pg/ml IL-1 beta, P = 0.036, respectively). However, the elevated levels of IL-1 beta were due to the higher cell number rather than to increased production by individual cells. Stimulation of oral PMN with recombinant granulocyte-macrophage colony stimulating factor did not enhance their cytokine production. In most instances. IL-1 beta production by oral PMN was dramatically greater than that of their blood counterparts. These findings suggest that oral PMN are an important source of IL-1 beta, which plays a central role in oral immunity and inflammatory disease states.
