Patients with Systemic Lupus Erythematosus have Reduced Numbers of Circulating Natural Interferon- alpha

Systemic lupus erythematosus (SLE) patients often have continuous production of interferon- alpha (IFN- alpha ), but production of in vitro IFN- alpha by peripheral blood mononuclear cells (PBMC) may be varyingly reduced. We here report that IFN- alpha production induced by Herpes simplex virus (HSV) in PBMC resembling immature dendritic cells and designated natural IFN- alpha producing cells (NIPC), was much more affected than that induced by sendai virus (SV) in monocytes. At the cell level, the frequency of HSV-activated NIPC was reduced 70-fold, but residual NIPC produced normal amounts of IFN- alpha (1-2 U/cell). The NIPC frequency increased 10-fold in SLE-PBMC, but not in control PBMC, when co-stimulated by the combination IFN- alpha - gamma and GM- CSF. No spontaneous IFN- alpha production by PBMCs was detected in SLE patients. While no SLE serum factor inhibiting IFN- alpha production was seen, sera of 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 endogenous IFN- alpha inducer, as well as because of lack of co-stimulatory cytokines. IFN- alpha produced in SLE could be of pathogenic significance, because autoimmune diseases develop in patients with infections or tumours during IFN- alpha therapy.