Exogenous IL-10 and IL-4 down-regulate IL-6 production by SLE-derived PBMC

The elevated expression of IL-6 and IL-10 may have an important role in SLE pathogenesis. IL-6 production by normal monocytes can be inhibited by IL-I O, and it has been suggested that SLE monocytes are refractory to this nega tive signal. To examine this possibility, the effects of regulatory factors on IL-6 expression by SLE PBMC (N = 51) were compared to effects on contro l PBMC (N = 21). We found that (1) exogenous rIL-10 and rIL-4 mediated redu ction of constitutive and lectin-induced IL-6 in monocytes of SLE patients as effectively as that of controls; (2) IL-6 mRNA decay was significantly d elayed in SLE with active disease (P < 0.001); (3) adding rIL-10 or neutral izing endogenous IL-IP and TNF-alpha down-regulated IL-6 mainly by destabil izing IL-6 transcripts, whereas exogenous IL-4 and TGF beta(1) down-regulat ed IL-6 transcriptionally; (4) time kinetics and levels of IL-10 were lower than those of IL-6 and IL-1 beta. Thus, contrary to a previous report, IL- 6 production by SLE PBMC responds normally to regulatory signals, and the I L-6 overexpression in SLE may he due, at least in part, to the kinetics and availability of regulatory cytokines. (C) 1999 Academic Press