Cytokines as therapeutic targets for the gastrointestinal manifestations of scleroderma: MCP-1 and IL-6
IL-6 levels are elevated in serum from SSc patients and correlate positively with skin thickness, making it a useful serological indicator of skin fibrosis . IL-6 production by SSc fibroblasts is significantly increased (30-fold) compared with normal fibroblasts and may be the result of constitutive binding of nuclear factors to the IL-6 promoter. Treatment with a combination of iloprost and cyclosporin A for one year significantly decreased serum IL-6 levels and resulted in morphological and functional improvement in the esophagus, skin and microvasculature.
Reduction of IL-6 and IL-4 decreased fibrosis in the TSK mouse model of SSc, resulting in marked reduction in skin thickness and serum levels of antinuclear antibodies , suggesting that IL-6 should be considered as part of an anticytokine approach to the treatment of SSc.
MCP-1 is a chemokine involved in recruiting and activating immune cells during inflammation and is expressed in SSc skin lesions by fibroblasts and infiltrating mononuclear cells. MCP-1 was elevated in serum from SSc patients where it correlated with the presence of pulmonary fibrosis.
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