Pretreatment of Human Vascular Smooth Muscle Cells with Interleukin-1 Enhances Interleukin-6 Production and Cell Proliferation (Action of IL-1 on Vascular Smooth Muscle Cells)

Abstract

Systemic vasculitis is an inflammatory disorder of blood vessels characterized by a perivascular mononuclear cell infiltration around the vessel and fibrinoid necrosis within vessel walls. Interleukin-I (IL-I) is a multipotent inflammatory mediator and affects several properties of vascular cells. To determine whether IL-1 could contribute to the pathogenesis of vascular diseases, we examined the effect of IL-l on B cell stimulatory factor-2/interleukin-6 (IL-6) production by cultured human vascular smooth muscle cells (SMC) and the proliferation of these cells. Supernatants of SMC stimulated IgM synthesis of human B cell line, SKW6-CL4 cells. This activity was increased (1.7 to 2.6-fold) when SMC were pretreated with IL-1 or calcium ionophore A23187 for 48 h, and was completely blocked by rabbit anti-human IL-6 antibodies. These IL-6 activities of the SMC supernatants were also assessed by using an IL-6 dependent murine hybridoma cell line, MH-60. BSF-2. In addition, we observed that pretreatment of SMC with IL-I for 48 h stimulated growth of SMC during the 96 h incubations, as assessed by cell number (p < 0.05). These results suggest that IL-l may contribute to the pathogenesis of inflammatory and immunological vasculitis by the augmentation of IL-6 release and growth of SMC.

Key Words:

• Vascular smooth muscle cells
• interleukin-6
• interleukin-I
• proliferation
• vasculitis