RESUMO
A defective chemokine motif in the HIV-1 Tat protein has been hypothesized to alter central nervous system cellular trafficking and inflammation, rendering HIV-1 subtype C less neuropathogenic than B. To evaluate this hypothesis, we compared biomarkers of cellular chemotaxis and inflammation in cerebrospinal fluid (CSF) and serum in individuals infected with HIV-1 subtypes B (n = 27) and C (n = 25) from Curitiba, Brazil. None had opportunistic infections. Chemokines (MCP-1, MIP-1α, MIP-1ß, RANTES, IP-10) and cytokines (TNF-α, IFN-γ, IL-1ß, IL-2, IL-4, IL-6, IL-7, IL-10) were measured using the multiplex bead suspension array immunoassays or ELISA HD. CSF and serum biomarker concentrations were compared between subtype B and C groups and HIV-positive and HIV-negative subjects (N = 19) using an independent group t test (unadjusted analysis) and linear regression (adjusted analysis), controlling for nadir CD4 and CSF and plasma HIV RNA suppression. CSF levels of cytokines and chemokines were significantly (p < 0.05) elevated in HIV-positive versus HIV-negative participants for 7/13 biomarkers measured, but levels did not differ for subtypes B and C. Serum levels were significantly elevated for 4/13 markers, with no significant differences between subtypes B and C. Although pleocytosis was much more frequent in HIV-positive than in HIV-negative individuals (27 vs. 0 %), subtypes B and C did not differ (32 and 22 %; p = 0.23). We did not find molecular evidence to support the hypothesis that intrathecal chemotaxis and inflammation is less in HIV-1 subtype C than in subtype B. Biomarker changes in CSF were more robust than in serum, suggesting compartmentalization of the immunological response to HIV.
Assuntos
Quimiocinas CC/líquido cefalorraquidiano , Quimiotaxia/imunologia , Infecções por HIV/líquido cefalorraquidiano , Interferon gama/líquido cefalorraquidiano , Interleucinas/líquido cefalorraquidiano , Leucocitose/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Adulto , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Estudos de Casos e Controles , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/virologia , Quimiocinas CC/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Interferon gama/sangue , Interleucinas/sangue , Leucocitose/sangue , Leucocitose/imunologia , Leucocitose/virologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , RNA Viral/imunologia , Fator de Necrose Tumoral alfa/sangue , Carga Viral/imunologiaRESUMO
We investigate the cytokine profile in the cerebrospinal fluid (CSF) and serum of patients with spinal cord schistosomiasis (SCS). Increased levels of IL-1beta, IL-4, IL-6 and IL-10 and low concentrations of TNF-alpha and IFN-gamma were observed in both CSF and serum. CSF showed higher levels of IL-4 and IL-6 when compared to the paired serum samples. A negative correlation between the concentrations of IL-10 and IFN-gamma was observed in the CSF. These findings suggest an inflammatory as well as a skewed type-2 immune response that probably occur both locally and systemically and may be involved in the pathogenesis of SCS.
Assuntos
Líquido Cefalorraquidiano/imunologia , Líquido Cefalorraquidiano/parasitologia , Citocinas/líquido cefalorraquidiano , Neuroesquistossomose/líquido cefalorraquidiano , Neuroesquistossomose/imunologia , Doenças da Medula Espinal/líquido cefalorraquidiano , Doenças da Medula Espinal/imunologia , Animais , Citocinas/análise , Citocinas/sangue , Regulação para Baixo/imunologia , Humanos , Interferon gama/análise , Interferon gama/sangue , Interferon gama/líquido cefalorraquidiano , Interleucinas/análise , Interleucinas/sangue , Interleucinas/líquido cefalorraquidiano , Mielite/líquido cefalorraquidiano , Mielite/imunologia , Mielite/parasitologia , Neuroesquistossomose/diagnóstico , Valor Preditivo dos Testes , Schistosoma mansoni/imunologia , Doenças da Medula Espinal/parasitologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Regulação para Cima/imunologiaRESUMO
No information about the levels of pro-inflammatory interleukins has been described in children with neurocysticercosis (NCC). The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-5, IL-6, and IL-12 in the cerebrospinal fluid from children with NCC were determined by enzyme-linked immunosorbent assay (ELISA). Twelve children with NCC, six with active and six with inactive disease, and six children without NCC were studied. TNF-alpha was undetectable in CSF from controls and five children with inactive NCC, whereas the levels were significantly higher (median 22.1 pg/ml; P = 0.008) in all children with active NCC. Levels of IL-6 were low in active and inactive NCC patients but two subjects with active subarachnoid disease had high levels. IL-5 and IL-12 were not detected. This study shows that high levels of TNF-alpha are present in CSF from children with active NCC. IL-6 levels are higher when infection occurs in the subarachnoid space.