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-10, and it has been suggested that SLE monocytes are refractory to this negative signal. To examine this possibility, the effects of regulatory factors on IL-6 expression by SLE PBMC (N = 51) were compared to effects on control PBMC (N = 21). We found that (1) exogenous rIL-10 and rIL-4 mediated reduction 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 delayed in SLE with active disease (P < 0.001); (3) adding rIL-10 or neutralizing endogenous IL-1 beta and TNF-alpha down-regulated IL-6 mainly by destabilizing IL-6 transcripts, whereas exogenous IL-4 and TGF beta 1 down-regulated 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 IL-6 overexpression in SLE may be due, at least in part, to the kinetics and availability of regulatory cytokines.
Linker-Israeli
M
M
Department of Medicine, Cedars-Sinai Medical Center Research Institute, California 90048, USA.
Honda
M
M
Nand
R
R
Mandyam
R
R
Mengesha
E
E
Wallace
D J
DJ
Metzger
A
A
Beharier
B
B
Klinenberg
J R
JR
D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4