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Superinduction of interleukin 8 mRNA in activated monocyte derived macrophages from rheumatoid arthritis patients
  1. Richard J T Rodenburga,b,
  2. Frank H J van den Hoogenb,
  3. Pilar Barrerab,
  4. Walther J van Venrooija,
  5. Leo B A van de Putteb
  1. aDepartments of Biochemistry, band Rheumatology, cUniversity of Nijmegen, Nijmegen, the Netherlands
  1. Dr R J T Rodenburg, Department of Biochemistry, University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands.


OBJECTIVE Synovial inflammation in patients with rheumatoid arthritis (RA) is characterised by the presence of large numbers of highly activated monocytes and macrophages. The importance of these cells in the aethiopathogenesis and prognosis of RA is increasingly recognised. The object of this report is to determine whether monocytes and monocyte derived macrophages of RA patients produce increased cytokine mRNA levels.

METHODS Monocyte derived macrophages from RA patients and healthy controls were cultured either in the absence or presence of lipopolysaccharide. The expression levels of the mRNAs encoding GAPDH, interleukin 1β (IL1β), IL8, and α2macroglobulin in these cells were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTS Activated monocyte derived macrophages from RA patients produce significantly higher IL8 mRNA levels than activated macrophages from healthy controls. By contrast, resting RA and control macrophages produce similar levels of IL8 mRNA. Culturing of activated macrophages in the presence of RA or control sera has no effect on the expression levels of IL8 mRNA. No significant differences between RA and control macrophages were observed in the expression levels of IL1β and α2 macroglobulin mRNAs.

CONCLUSION These data indicate that the increased IL8 mRNA production capacity of RA macrophages upon activation is an intrinsic property of these cells, and is not attributable to factors present in the circulation. Based on these observations, it is postulated that this innate hyper-responsiveness of RA macrophages contributes to the high IL8 levels present in the synovial fluid of rheumatoid joints, and is implicated in the chemotactic gradient leading to the homing of leucocytes to the joints.

  • rheumatoid arthritis
  • monocytes
  • macrophages
  • cytokines

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