Interleukin-1 dysregulation is an intrinsic defect in macrophages from MRL autoimmune-prone mice.
Macrophages (M phi) from pre-diseased autoimmune-prone MRL mice (both MRL/+ and MRL/lpr) dramatically underproduce the cytokine interleukin-1 (IL-1) in comparison to M phi from a number of normal strains. In this study we show that IL-1 dysregulation by MRL M phi 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 M phi 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 M phi 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 M phi from MRL autoimmune-prone mice.
Levine
J S
JS
Renal Section, Boston University Medical Center, MA.
Pugh
B J
BJ
Hartwell
D
D
Fitzpatrick
J M
JM
Marshak-Rothstein
A
A
Beller
D I
DI
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011828:Radiation Chimera / Q000276:immunology
D007375:Interleukin-1; D012333:RNA, Messenger