RESUMO
BACKGROUND: Interferon beta has been approved for the treatment of multiple sclerosis (MS). It is believed that immunomodulatory rather than antiviral activity of interferon beta is responsible for disease amelioration. The impact of interferon beta on the chemoattraction of immune cells has not been fully addressed. OBJECTIVE: To address the influence of interferon beta on the expression of chemokines and their receptors in a standardized setting. DESIGN: The expression of 14 chemokines and 14 chemokine receptor genes was determined by quantitative real-time polymerase chain reaction from fresh blood samples. SETTING: Outpatient units in Germany. Patients Untreated and interferon beta-treated patients with MS who tested positive and negative for neutralizing antibodies (NABs) were recruited from August 24, 2006, through December 15, 2006, for the initial study and from March 12, 2007, through April 2, 2007, for the validation study. MAIN OUTCOME MEASURES: Gene expression and serum chemokine protein levels. RESULTS: CCL1, CCL2, CCL7, CXCL10, CXCL11, and CCR1 gene expression was strongly upregulated in interferon beta-treated, NAB-negative MS patients. In contrast, gene expression in interferon beta-treated, NAB-positive MS patients did not differ from untreated control donor individuals. Antibody titers inversely correlated with chemokine and chemokine receptor gene expression. Accordingly, serum chemokine protein levels of interferon beta-treated, NAB-negative MS patients were significantly higher than in untreated or interferon beta-treated, NAB-positive MS patients. CONCLUSIONS: We demonstrate that interferon beta strongly upregulates a set of chemokines and CCR1 in peripheral immune cells. The peripheral upregulation of these chemokines may reduce the chemoattraction of immune cells to the central nervous system and thus add to the therapeutic effects of interferon beta.
Assuntos
Quimiocinas/biossíntese , Imunossupressores/uso terapêutico , Interferon Tipo I/uso terapêutico , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Adulto , Autoanticorpos/análise , Autoanticorpos/biossíntese , Quimiocinas/sangue , Quimiocinas/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imunossupressores/efeitos adversos , Interferon Tipo I/efeitos adversos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/metabolismo , Testes de Neutralização , Pacientes Ambulatoriais , RNA/biossíntese , Receptores CCR1/biossíntese , Receptores CCR1/genética , Receptores de Quimiocinas/biossíntese , Receptores de Quimiocinas/genética , Proteínas Recombinantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Regulação para Cima/efeitos dos fármacos , Adulto JovemRESUMO
Inflammatory diseases of the central nervous system (CNS) are characterized by cerebrospinal fluid (CSF) pleocytosis often involving the recruitment of B cells. Little is still known about B cells that are found in the CSF during neuroinflammation. To address the phenotype of these B cells, we studied the distribution of the major B cell subsets in peripheral blood (PB) and CSF of 25 patients with inflammatory diseases of the nervous system by flow cytometry. Six different B cell subsets were identified in PB and CSF according to the surface expression of IgM, IgD, CD27 and CD19. In all patients analysed, memory B cells outnumbered naïve B cells in the CSF, whereas naïve B cells were more prevalent in PB. The accumulation of memory B cells in the CSF was largely due to the recruitment of IgM-IgD- class switched memory B cells. The distribution of IgM+IgD+, IgM-IgD+, IgM+IgD- memory cells and immature cells did not differ significantly between CSF and PB. These findings demonstrate a selective recruitment of IgM-IgD- memory B cells to the CSF suggesting a specific role of these cells during neuroinflammation.
