Superinduction of interleukin 8 mRNA in activated monocyte derived macrophages from rheumatoid arthritis patients

Objective-Synovial inflammation in patients with rheumatoid arthritis (RA) is characterised by the presence of large numbers of highly activated monoc ytes and macrophages. The importance of these cells in the aethiopathogenes is and prognosis of RA is increasingly recognised. The object of this repor t 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 1 beta (IL1 beta ), IL8, and alpha(2) macroglobulin in these cells were analysed by reverse transcriptase-polymerase chain reaction (RT-FCR). Results-Activated monocyte derived macrophages from RA patients produce sig nificantly higher IL8 mRNA levels than activated macrophages from healthy c ontrols. Ey contrast, resting RA and control macrophages produce similar le vels 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 sign ificant differences between RA and control macrophages were observed in the expression levels of IL1 beta and alpha(2) macroglobulin mRNAs. Conclusion-These data indicate that the increased IL8 mRNA production capac ity of RA macrophages upon activation is an intrinsic property of these cel ls, and is not attributable to factors present in the circulation. Eased on these observations, it is postulated that this innate hyperresponsiveness of RA macrophages contributes to the high IL8 levels present in the synovia l fluid of rheumatoid joints, and is implicated in the chemotactic gradient leading to the homing of leucocytes to the joints.