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Doctoral Thesis
DOI
https://doi.org/10.11606/T.17.2020.tde-19082020-231632
Document
Author
Full name
Caetano Galvão Petrini
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2020
Supervisor
Committee
Quintana, Silvana Maria (President)
Bonato, Vania Luiza Deperon
Murta, Eddie Fernando Candido
Reis, Francisco José Cândido dos
Title in Portuguese
Perfil intralesional de citocinas em lesões intraepiteliais de baixo e alto grau do colo uterino
Keywords in Portuguese
Citocinas
Colo uterino
Lesão intraepitelial cervical
Papiloma vírus humano
Abstract in Portuguese
A infecção persistente pelo HPV está relacionada ao desenvolvimento de lesões intraepiteliais de alto grau e carcinoma invasor do colo uterino. A resposta imune do hospedeiro desempenha um papel fundamental na eliminação ou persistência do HPV. A maioria dos estudos sobre a resposta imune local ao HPV realizou a coleta de muco cervical para a análise quantitativa de citocinas secretadas; no entanto, essa amostragem pode refletir apenas a resposta das células no epitélio da superfície, enquanto as células localizadas no interior do tecido podem liberar citocinas diferentes associadas à infecção pelo HPV. Este estudo teve como objetivo quantificar as citocinas: inrterleucina (IL-) 2, IL-4,IL-10, IL-12,IL-17A, IL-23 e INF-γ em amostras de biópsias de colo uterino de mulheres com achados colposcópicos anormais e comparar suas concentrações entre amostras com laudo anatomopatológico de Lesão Intraepitelial de Baixo Grau (LIEBG), Lesão Intraepitelial de Alto Grau (LIEAG) e amostras de biópsias que não revelaram lesão intraepitelial (Ausência de Lesão Intraepitelial - ALIE). Para cumprir este objetivo foi realizado um estudo observacional analítico quantificando estas citocinas através do método Elisa Luminex em amostras de lesões de colo uterino de 141pacientes. Para verificar se houve diferença nos níveis de citocinas entre os grupos foi utilizado o teste de Kruskal-Wallis. As 141 amostras incluíram 90 LIEAG, 22 LIEBG e 29 ALIE. Os níveis de IL-2 foram significativamente maiores no grupo ALIE do que no LIEBG ou no LIEAG (p = 0,0001) e os níveis de IL-23 foram significativamente maiores no ALIE do que no LIEAG (p = 0,003). Nosso estudo mostrou que citocinas pró-inflamatórias importantes, IL-2 e IL-23, são reguladas negativamente em lesões por HPV. Coletando amostras do ponto do local da lesão, fornecemos uma compreensão do mecanismo de resposta imune no microambiente das lesões intraepiteliais cervicais.
Title in English
Intralesional cytokine profile in low and high grade cervix intraepithelial lesions
Keywords in English
Cervix
Cytocines
Human papilloma virus
Intraepithelial lesions
Abstract in English
Infection with persistent high-risk HPV types is associated with high-grade intraepithelial lesions and invasive cervical cancer. The host immune response plays a key role in whether HPV clears or persists. Most studies on local immune response to HPV collect cervical mucus in order to quantify secreted cytokines; however, this sampling may reflect only the response from cells on the surface epithelium, whereas cells located inside the tissue can release different cytokines associated with HPV infection. This study aimed to measure cervical levels of cytokines interleukin (IL-) 2, IL-4, IL-10, IL-12, IL-17 and IL-23, and interferon-γ (INF-γ), in biopsy specimens from women with abnormal colposcopic findings and compare their concentrations in histologically confirmed LSIL (low-grade intraepithelial lesion), HSIL (high-grade intraepithelial lesion), and specimens negative for intraepithelial lesion (no intraepithelial lesion, NSIL). A cross-sectional study of cervical biopsy specimens from 141 women with cervical lesions examined the cytokine profile, using the Luminex/Elisa assay. Differences in cytokine levels among the cervical lesion groups were assessed using the Kruskal-Wallis test. The 141 specimens included 90 HSIL, 22 LSIL, and 29 NSIL. IL-2 levels were significantly higher in NSIL than in LSIL or in HSIL (p=0.0001) and IL-23 levels were significantly higher in NSIL than in HSIL (p=0.003). Our study showed that important pro-inflammatory cytokines, IL-2 and IL- 23, are downregulated in HPV lesions. By collecting samples from the lesion site point, we provide an understanding of immune response mechanism in microenvironment of cervical intraepithelial lesions.
 
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Publishing Date
2020-10-22
 
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