Interleukin‐1 dysregulation is an intrinsic defect in macrophages from MRL autoimmune‐prone mice

摘要

AbstractMacrophages (Mϕ) from pre‐diseased autoimmune‐prone MRL mice (both MRL/+ and MRL/1pr) dramatically underproduce the cytokine interleukin‐1 (IL‐1) in comparison to Mϕ from a number of normal strains. In this study we show that IL‐1 dysregulation by MRL Mϕ is fully expressed at birth, and that this defect does not change with time or the development of disease. We also constructed adult irradiation chimeras (consisting of A/J → MRL and MRL → A/J mice), and show that Mϕ isolated from these chimeras display a pattern of IL‐1 production indistinguishable from that of the donor strain controls. Moreover, when we constructed a mixed chimera (A/J + MRL → A/J), the A/J and MRL Mϕ coexisting within the same animal retained their individual patterns of IL‐1 production when isolated by negative selection. Taken together, these results provide the first substantive evidence for an intrinsic defect (IL‐1 dysregulation) in Mϕ fro