The restoration of IL-6 “trans-signaling” by administration of soluble IL-6Ra resulted in lethality in the IL-6Ra-deficient mice, whereas the neutralization of trans-signaling by administration of soluble gp130 increased the survival in IL-6Ra-sufficient mice, providing convincing evidence for a pathogenic role of IL-6 by trans-signaling in this model [6] However, older studies in different mouse models, including the P. berghei ANKA experimental cerebral malaria model, found no evidence for a causal role of IL-6 in the pathogenesis of severe malaria [7]. The gene discussed is IL6ST; the disease is malaria.