Calcium Channel Blockers Activate the Interleukin-6 Gene Via the Transcription Factors NF-IL6 and NF-κB in Primary Human Vascular Smooth Muscle Cells

We read with interest the recent study by Eickelberg et al 1 concerning the activation of the interleukin-6 (IL-6) gene via the transcription factors NF-IL6 and NF-B by calcium channel blockers (CCBs) in human vascular smooth muscle cells (VSMCs). CCBs reduce the severity of experimentally induced atherosclerosis, and some clinical trials suggest that they retard or impede the progression of atherosclerosis in humans. We previously reported that IL-6 stimulates the proliferation of VSMCs. 2 Thus, the study by Eickelberg et al suggests that CCBs promote atherogenesis by inducing IL-6. However, Eickelberg et al cite the study by Lotz and Guerne. In this study, IL-6 induced the expression of the tissue inhibitor of metalloproteinase-1 (TIMP-1), an endogenous inhibitor of matrix metalloproteinases (MMPs), in human connective tissue cells. Eickelberg et al 1 proposed that the local induction of IL-6 in the arterial vessel wall by CCBs essentially reduced atherosclerotic progression by inducing the expression of tissue TIMPs.