RESUMO
PROBLEM: We compared the frequency of intra-amniotic infection in preterm labor (PL) with women not in labor, and correlated infection with amniotic fluid (AF) cytokines. Detailed identification of species, especially mycoplasmata, was tried to improve our understanding of the pathogenesis of PL. METHOD OF STUDY: AF from 20 women with PL and 20 controls were evaluated. Infection was detected by PCR for Mycoplasma hominis, Ureaplasma urealyticum and 16S rRNA bacterial gene, which was cloned and sequenced for bacterial identification. Interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor (TNF)-α levels were measured by ELISA. RESULTS: Frequency of intra-amniotic infection is higher in PL (40.0%). Sequencing-based method identified Bacteroides fragilis, Prevotella bivia and Leptotrichia amnionii, in addition to Mycoplasma species detected by PCR. AF infection correlated with increased IL-1ß and IL-6 levels. CONCLUSION: The frequency of intra-amniotic infection, especially M. hominis, in PL women who delivered with 7 days, is high and correlates with high IL-1ß and IL-6 levels, but not IL-8.
Assuntos
Líquido Amniótico/metabolismo , Bactérias Anaeróbias Gram-Negativas/fisiologia , Infecções por Bactérias Gram-Negativas/imunologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Infecções por Mycoplasma/imunologia , Mycoplasma hominis/fisiologia , Trabalho de Parto Prematuro/imunologia , Infecções por Ureaplasma/imunologia , Ureaplasma urealyticum/fisiologia , Líquido Amniótico/imunologia , Líquido Amniótico/microbiologia , Feminino , Bactérias Anaeróbias Gram-Negativas/patogenicidade , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Interleucina-8/metabolismo , Infecções por Mycoplasma/epidemiologia , Mycoplasma hominis/patogenicidade , Trabalho de Parto Prematuro/epidemiologia , Trabalho de Parto Prematuro/microbiologia , Gravidez , Prevalência , RNA Ribossômico 16S/análise , Análise de Sequência de RNA , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Infecções por Ureaplasma/epidemiologia , Ureaplasma urealyticum/patogenicidadeRESUMO
Increased risk of preterm labor has been linked to cervicovaginal infection with Ureaplasma urealyticum and group B streptococci. Although various experimental models have been developed to study the role of amniochorion infection in preterm labor, they typically exclude the initial interaction between intrauterine leukocytes (recruited from decidual vessels into the avascular fetal membranes) and infecting bacteria. In this work, we ascertained whether inflammatory molecules secreted by bacterium-activated intrauterine leukocytes stimulate the amniochorion production of mediators involved in human labor. Using a two-step process beginning with placental circulating leukocytes as a proxy for intrauterine leukocytes, we found that coincubation of amniochorion explants with plasma from placental whole blood preincubated with group B streptococci resulted in a significant increase in tumor necrosis factor alpha (TNF-α) and matrix metalloproteinase 9 (MMP-9) levels in tissue. Extensive changes in the connective tissue arrangement and a decrease in collagen content demonstrated the degradation of the extracellular matrix following this treatment. In contrast, plasma from blood preconditioned with U. urealyticum induced a highly significant secretion of interleukin-1ß (IL-1ß) and prostaglandin E(2) (PGE(2)) by the amniochorion without changes in the extracellular matrix organization or content. These data demonstrate that group B streptococci induce degradation of the amniochorion as a result of MMP-9 production, probably via TNF-α, whereas U. urealyticum stimulates the secretion of PGE(2), probably via IL-1ß, potentially stimulating myometrial contraction. Our study provides novel evidence that the immunological cells circulating within the uterine microenvironment respond differentially to an infectious agent, triggering alternative molecular signaling pathways leading to human labor.