RESUMO
Proinflammatory cytokines were reported to be implicated in the pathogenesis of perinatal white matter lesions. The authors document for the first time the in situ detection of interleukin-2 and interleukin-2 receptor (IL-2R) in these human white matter lesions. These results suggest that interleukin-2, reported to be toxic to oligodendrocytes and myelin, could play a role in the molecular cascade leading to white matter damage in periventricular leukomalacia.
Assuntos
Encéfalo/metabolismo , Encéfalo/patologia , Recém-Nascido/metabolismo , Recém-Nascido Prematuro , Interleucina-2/biossíntese , Citocinas/análise , Citocinas/biossíntese , Feminino , Humanos , Mortalidade Infantil , Recém-Nascido Prematuro/metabolismo , Interleucina-2/análise , Masculino , Estatísticas não ParamétricasRESUMO
BACKGROUND: Periventricular leukomalacia (PVL) affects the developing white matter of neonatal brain. Inflammatory and infectious conditions are implicated in the cause of PVL. METHODS: The authors investigated the in situ expression of proinflammatory cytokines (interleukin-1beta and -6, tumor necrosis factor alpha [TNFalpha]), adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1) and inflammatory cell markers (CD68, leukocyte common antigen, human leukocyte antigen II) in 19 neonatal brains with PVL. The authors compared the findings with matched non-PVL brains. RESULTS: The inflammatory reaction detected at the early stage of PVL extends until the latest phase of cystic cavitation, though at an attenuated level. There is high expression of TNFalpha and to a lesser extent interleukin-1beta; interleukin-6 remains undetectable. Cytokine immunoreactivity is detected in PVL cases both with and without infection. However, cytokine production was higher with infection. A different pattern of cytokine expression was observed in anoxic brains without PVL: TNFalpha immunoreactivity was significantly lower than the PVL group. CONCLUSIONS: An immune-mediated inflammatory process may play a role in PVL. TNFalpha, a myelinotoxic factor, may be the major mediator.
Assuntos
Encéfalo/imunologia , Encéfalo/metabolismo , Citocinas/metabolismo , Encefalite/imunologia , Encefalite/metabolismo , Leucomalácia Periventricular/imunologia , Leucomalácia Periventricular/metabolismo , Antígenos de Superfície/metabolismo , Encéfalo/patologia , Paralisia Cerebral/imunologia , Paralisia Cerebral/metabolismo , Paralisia Cerebral/patologia , Feminino , Humanos , Recém-Nascido , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Leucomalácia Periventricular/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Neuroglia/metabolismo , Neuroglia/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Mice inoculated weekly with Plasmodium berghei sporozoites while under treatment with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, developed protective immunity against subsequent challenge with this parasite. The percentage of mice protected was similar whether DFMO alone (55%) or DFMO + chloroquine (65%) was used. With chloroquine alone, only 12% of mice were protected. This protection was long-lasting (at least six months). The immunity protected against sporozoites but not against erythrocytic form inoculation. It is suggested that this protection is induced by antigens released from exoerythrocytic schizonts whose further development is inhibited by DFMO.
