PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS HAVE REDUCED NUMBERS OF CIRCULATING NATURAL INTERFERON-ALPHA-PRODUCING CELLS

Systemic lupus erythematosus (SLE) patients often have continuous prod uction of interferon-alpha (IFN-alpha), but production of in vitro IFN -alpha by peripheral blood mononuclear cells (PBMC) may be varyingly r educed. We here report that IFN-alpha production induced by Herpes sim plex virus (HSV) in PBMC resembling immature dendritic cells and desig nated natural IFN-alpha producing cells (NPPC), was much more affected than that induced by sendai virus (SV) in monocytes. At the cell leve l, the frequency of HSV-activated NIPC was reduced 70-fold, but residu al NIPC produced normal amounts of IFN-alpha (1-2 U/cell). The NIPC fr equency increased 10-fold in SLE-PBMC, but not in control PBMC, when c ostimulated by the combination IFN-alpha, -gamma and GM-CSF. No sponta neous IFN-alpha production by PBMCs was detected in SLE patients. Whil e no SLE serum factor inhibiting IFN-alpha production was seen, sera o f four out of 11 SLE patients induced IFN-alpha production in healthy control PBMC. We propose that the number of NIPC in SLE are reduced in blood because of recruitment to tissues and activation by an endogeno us IFN-alpha inducer, as well as because of lack of co-stimulatory cyt okines. IFN-alpha produced in SLE could be of pathogenic significance, because autoimmune diseases develop in patients with infections or tu mours during IFN-alpha therapy. (C) 1998 Academic Press