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

Eur J Immunol. 1993 Nov;23(11):2951-8. doi: 10.1002/eji.1830231134.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / metabolism
  • Interleukin-1 / biosynthesis*
  • Interleukin-1 / genetics
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C3H
  • Mice, Mutant Strains
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radiation Chimera / immunology

Substances

  • Interleukin-1
  • RNA, Messenger