Given that anti-IL-6 and anti-IL6R inhibition may lead to unwanted neutropenia and infection, targeting IL-6 trans-­signaling without disrupting classical signaling pathways may prove to be a superior approach in SLE as many anti-inflammatory and regulatory mechanisms mediated by IL-6 classic signaling will not be impacted (Figure 3D) (162, 163, 178). This evidence concerns the gene IL6 and infection.