Hyper-IL-6 has been used to test which cells depend on Interleukin-6 trans-signaling in their response to the cytokine Interleukin-6. To this end, cells were treated with Interleukin-6 and alternatively with Hyper-IL-6. Cells, which respond to Interleukin-6 alone do express an Interleukin-6 receptor whereas cells, which only respond to Hyper-IL-6 but not to  Interleukin-6 alone depend in their response to the cytokine on Interleukin-6 trans-signaling. It turned out that hematopoietic stem cells, neural cells, smooth muscle cells and endothelial cells are typical target cells of Interleukin-6 trans-signaling.