Introduction: Multiple sclerosis (MS) is a chronic inflammatory- demyelinating disease of central nervous system (CNS) with variable onset and progression. Active lesions in the CNS of MS patients are characterized by perivascular infiltrates, constituted by T activated lymphocytes and antigen presenting cells (B cells and monocytes). These blood-borne cells expressing CD40L and CD4O respectively were recruited by chemoattractant factors as MCP—1 and locally produced Th1 cytokines contribute to disease progression, while Th2 cytokines could be involved in remission. Aim of this study is to clarify if observed intrathecal "cytokine storm" may be also reflected in peripheral blood. We evaluated the behaviour of serum Th1 (IL-12, IFN-gamma, TNF—alpha, MCP-1) and Th2 (lL-10, TGF—beta) cytokines and CD40 and CD40L membrane expression on peripheral blood mononuclear ceIls.(PBMC) in active and stable MS patients. Methods: 24 MS patients were divided in two groups: clinically active (16) and stable (8). 10 other neurological disease (OND) patients and 8 healthy subjects (HS) were used as controls. PBMC were assayed with anti-CD40 and anti-CD4OL MoAb. Cytokines were determined by ELISA kits. Results and Discussion: Our results showed that serum |L-12, TNF-alpha, IFN-gamma and MCP-1 and CD40 and CD40L membrane expression on PBMC were significantly higher in active MS patients than in stable and OND groups. By contrast in stable patient serum TGF-beta and lL-10 values were significantly increased than in active and OND groups. HS demonstrated no changes of all parameters. Our data suggest that in MS patient serum occurs, as in the CNS, a "cytokine storm" with an increase of inflammatory cytokines during active disease. We hypothesize this increase could be due to the involvement of circulating monocytes and T cells, activated by unidentified and repeated antigenic stimulations, as evidenced also by higher expression of CD40 and CD4OL on membrane PBMC. By contrast TGF-beta and IL-10 elevated serum levels suggested a switch from Th1 to Th2 pattern in stable MS patients.

Serum cytokine dysregulation in multiple sclerosis patients

SOFO, Vincenza;DI BELLA, Paolo;SALMERI, Francesca Maria;BITTO, ALESSANDRA;SESSA, Edoardo;BRAMANTI, Placido
2004

Abstract

Introduction: Multiple sclerosis (MS) is a chronic inflammatory- demyelinating disease of central nervous system (CNS) with variable onset and progression. Active lesions in the CNS of MS patients are characterized by perivascular infiltrates, constituted by T activated lymphocytes and antigen presenting cells (B cells and monocytes). These blood-borne cells expressing CD40L and CD4O respectively were recruited by chemoattractant factors as MCP—1 and locally produced Th1 cytokines contribute to disease progression, while Th2 cytokines could be involved in remission. Aim of this study is to clarify if observed intrathecal "cytokine storm" may be also reflected in peripheral blood. We evaluated the behaviour of serum Th1 (IL-12, IFN-gamma, TNF—alpha, MCP-1) and Th2 (lL-10, TGF—beta) cytokines and CD40 and CD40L membrane expression on peripheral blood mononuclear ceIls.(PBMC) in active and stable MS patients. Methods: 24 MS patients were divided in two groups: clinically active (16) and stable (8). 10 other neurological disease (OND) patients and 8 healthy subjects (HS) were used as controls. PBMC were assayed with anti-CD40 and anti-CD4OL MoAb. Cytokines were determined by ELISA kits. Results and Discussion: Our results showed that serum |L-12, TNF-alpha, IFN-gamma and MCP-1 and CD40 and CD40L membrane expression on PBMC were significantly higher in active MS patients than in stable and OND groups. By contrast in stable patient serum TGF-beta and lL-10 values were significantly increased than in active and OND groups. HS demonstrated no changes of all parameters. Our data suggest that in MS patient serum occurs, as in the CNS, a "cytokine storm" with an increase of inflammatory cytokines during active disease. We hypothesize this increase could be due to the involvement of circulating monocytes and T cells, activated by unidentified and repeated antigenic stimulations, as evidenced also by higher expression of CD40 and CD4OL on membrane PBMC. By contrast TGF-beta and IL-10 elevated serum levels suggested a switch from Th1 to Th2 pattern in stable MS patients.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11570/1581461
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