Impaired production of IL-12 in systemic lupus erythematosus. I. Excessive production of IL-10 suppresses production of IL-12 by monocytes.
Interleukin 12 (IL-12) plays a crucial role in defensive immune responses, modulation of cytokine production and is involved in the pathogenesis of some autoimmune diseases. The authors investigated whether decreased in vitro production of IL-12 occurs in systemic lupus erythematosus (SLE), in which the cytokine secreting pattern is predominantly type 2. IL-12 production by SLE peripheral blood mononuclear cells (PBMC) was significantly impaired compared with normal PBMC, and this was not due to decreased numbers of monocytes. After depletion of non-adherent cells from PBMC, monocytes of SLE patients produced significantly less IL-12 than those of controls, but IL-12 levels in SLE and control non-adherent cells supernatants were not significantly different. Exogenous recombinant (r)IL-10 strongly inhibited IL-12 production by both SLE and normal PBMC and anti-IL-10 neutralizing antibody significantly reversed the IL-12 deficiency of SLE PBMC and SLE monocytes, while not affecting normal PBMC. Recombinant interferon gamma (rIFN-gamma) considerably enhanced IL-12 production in both SLE and normal PBMC, but it did not significantly reverse the inhibitory effect of rIL-10 on IL-12 production. IL-12 production was significantly lower in patients with active SLE than those in remission. These results suggest that SLE monocytes may be deficient in IL-12 production and that this is secondary to abnormal production of various cytokines, especially excessive production of IL-10.
Liu
T F
TF
Department of Pathology, University of Hong Kong, Hong Kong.
Jones
B M
BM
D001402:B-Lymphocytes / Q000378:metabolism; D001681:Biological Assay / Q000592:standards; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D009500:Neutralization Tests
D016207:Cytokines; D015850:Interleukin-6; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4