Perfil de biomarcadores inflamatórios de hidrocefalia infantil tumoral e não-tumoral: influência da etiologia na resposta sistêmica

Abstract

Hydrocephalus is a ventricular dilatation due to CSF obstruction, which could progress to intracranial hypertension (ICH), an event often fatal. The systemic and CSF cytokines evaluation could improve the knowledge from ICH damage, especially when chronic hydrocephalus or obstructive tumors are involved. In children, it´s an innovation when the immunological phenotype of tumors are analyzed in this issue. There are few studies trying to compare the response of cytokines in brain injuries associated or not to tumors. The goal was to investigate the immunological aspects of tumoral (benign and malignant) and non-tumor hydrocephalus in children submitted to ventricular shunt due to HIC in a tertiary pediatric hospital from Fortaleza - CE, under a prospective and observational study. We selected chidren with tumoral hydrocephalus, non-tumoral hydrocephalus undergoing ventricular shunt, and healthy patients. Blood and CSF samples were collected during surgery and measured: IL-6, IL-10, IL-18 and IL-33 by Elisa method. Tumor biopsies were analyzed by immunohistochemistry (CD4, CD8, CD20, CD45, CD45RO, CD68 and GFAP markers) and immunofluorescence (double labeling for M1: IBA1 + CD40, and for M2:IBA1 + CD206. 8 patients with benign tumor were analyzed: astrocytoma pilocytic n=3; ependymoma n=2; choroid plexus papilloma, n=1, neurocytoma n=1, and craniopharyngioma, n=1); six with malignant tumor (meduloblastoma, n=4; glioblastoma, n=1; and pinealoblastoma, n=1) , 14 non-tumor hydrocephalus patients and 12 controls. In our results, despite of better outcome, the non-tumor hydrocephalus group showed an increase in CRP, while the tumor groups showed a delay in improvement after shunt, the lowest CRP and leukometry increases were observed in benign tumor group. Regarding plasma cytokines, an increase in IL-10 was observed in the groups with hydrocephalus, independent of the cause, compared to the control group (p=0.002), IL-6 showed lower values in the benign tumour group, comparing to other groups (p=0 .001). In CSF, IL-18 had higher values in the hydrocephalus groups, independent of the cause, compared to controls (p=0.002). In immunohistochemical evaluation, higher expressions of CD8 and CD45RO were observed in malignant tumors, and in the immunofluorescence evaluation, the typical M1 polarization occurred in malignant tumors and there was a balance in the CD40/CD206 ratio in benign tumors. The research data allow us to conclude that the systemic response due to ICH was attenuated in tumoral hydrocephalus, it was showed more evident in benign tumors, and in non-tumor hydrocephalus, this change was minimal. There was a difference in cytokine expression with increased serum IL-10 in patients with hydrocephalus, independent of cause, and decreased serum IL-6 in benign tumor, which may explain the systemic response. It was added to high CSF IL -18 in all hydrocephalus groups, possibly by a brain injury reflex from ICH. Malignant tumors showed M1 polarization to macrophages/microglia and high cytotoxic lymphocytes and memory cells, however, these findings were not related to the expected systemic response. We produced a highlight research, because the association of ICH (regardless of the cause), plasma and CSF cytokines and histology is highnew in literature, especially in neuropediatrics, we destached that there are few animal studies in this focus.