Augmented production of chemokines (monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta) in patients with systemic sclerosis: MCP-1 and MIP-1alpha may be involved in the development of pulmonary fibrosis

Abstract

To determine the role of chemokines in the pathogenesis of systemic sclerosis (SSc), we examined serum levels, spontaneous production by peripheral blood mononuclear cells (PBMC), and histological distribution in the affected skin, of MCP-1, MIP-1alpha and MIP-1beta in SSc patients. Serum levels of these chemokines were examined by ELISA in 58 patients with SSc and 20 normal controls. The levels of these chemokines in culture supernatants from PBMC were also measured by ELISA. Serum levels and spontaneous production levels by PBMC of MCP-1, MIP-1alpha, and MIP-1beta were significantly elevated in patients with SSc compared with normal controls. Elevated serum levels of MCP-1 and MIP-1alpha significantly correlated with the presence of pulmonary fibrosis. MCP-1 expression in the skin of SSc was immunohistochemically examined using anti-MCP-1 MoAb. MCP-1 was strongly expressed in the epidermis, inflammatory mononuclear cells, and vascular endothelial cells in the sclerotic skin of SSc patients, but not expressed in any control skin. Furthermore, the MCP-1 expression in inflammatory mononuclear cells and endothelial cells significantly correlated with earlier onset of SSc. Thus, MCP-1, MIP-1alpha and MIP-1beta may be involved in the disease process, possibly by augmenting leucocyte migration into the affected tissues in SSc. Furthermore, MCP-1 and MIP-1alpha may play an important role in the development of pulmonary fibrosis in SSc.

Fig. 1

Serum levels of MCP-1 (a), MIP-1α (b), and MIP-1β (c) in normal controls, patients with limited cutaneous systemic sclerosis (lSSc), and diffuse cutaneous SSc (dSSc). The short bar indicates the median value in each group. A broken line indicates detection limit and the number below the line indicates the number of patients with undetectable levels.

Fig. 2

Production levels of MCP-1 (a), MIP-1α (b), and MIP-1β (c) by cultured peripheral blood mononuclear cells from normal controls and patients with limited cutaneous systemic sclerosis (lSSc) and diffuse cutaneous systemic sclerosis (dSSc). The short bar indicates the median value in each group.

Fig. 3

Immunohistochemical expression of MCP-1 in epidermis of skin tissues from a patient with systemic sclerosis (SSc) (a) and from a normal control (b). Immunohistochemical expression of MCP-1 in vascular endothelial cells (c) of skin tissues from a patient with SSc and from a normal control (d). Expression of MCP-1 in inflammatory mononuclear cells (e) from a patient with SSc is also shown (× 800).