1. Exogenous IL-10 and IL-4 down-regulate IL-6 production by SLE-derived PBMC
- Author
-
Mariana Linker-Israeli, Richa Nand, James R. Klinenberg, Allan L. Metzger, Motoko Honda, Rangu Mandyam, Emebet Mengesha, Daniel J. Wallace, and Brenda Beharier
- Subjects
Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Down-Regulation ,In Vitro Techniques ,Peripheral blood mononuclear cell ,Pathogenesis ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Lupus Erythematosus, Systemic ,RNA, Messenger ,Interleukin 6 ,TGF beta 1 ,Interleukin 4 ,biology ,business.industry ,Interleukin-6 ,Monocyte ,Middle Aged ,Recombinant Proteins ,Interleukin-10 ,Interleukin 10 ,Kinetics ,medicine.anatomical_structure ,Cytokine ,Endocrinology ,Case-Control Studies ,biology.protein ,Leukocytes, Mononuclear ,Cytokines ,Female ,Interleukin-4 ,business - Abstract
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.
- Published
- 1999