The combination of apoptotic U937 cells and lupus IgG is a potent IFN-alpha inducer

Patients with active systemic lupus erythematosus (SLE) have signs of an on going IFN-alpha production, that may be of pathogenic significance in the d isease, We previously showed that SLE patients have an IFN-alpha -inducing factor in blood, probably consisting of complexes containing anti-DNA Abs a nd immunostimulatory DNA, The DNA component could be derived from apoptotic cells, because SLE patients have been reported to have both increased apop tosis and reduced clearance of apoptotic cell material, In the present stud y, we therefore investigated whether apoptotic cells, together with Ige fro m SLE patients, could act as an IFN-alpha inducer in normal PBMC in vitro. We found that apoptotic cells of the myeloid leukemia cell line U937 as wel l as four other cell lines (MonoMac6, H9, Jurkat, U266) could induce IFN-al pha production in PBMC when combined with IgG from SLE patients. The IFN-al pha production by PBMC was much enhanced when PBMC were costimulated by IFN -alpha 2b, The ability of IgG from different SLE patients to promote IFN-al pha induction by apoptotic U937 cells was associated with the presence of a nti-ribonucleoprotein Abs, but not clearly with occurrence of anti-DNA Abs, These results suggest that apoptotic cells in the presence of autoantibodi es can cause production of a clearly immunostimulatory cytokine, which is I FN-alpha, This mechanism for induction of IFN-alpha production could well b e operative also in vivo, explain the IFN-alpha production seen in SLE pati ents, and be important in the pathogenesis of SLE.