Impaired production of IL-12 in systemic lupus erythematosus. I. Excessive production of IL-10 suppresses production of IL-12 by monocytes

Cytokine. 1998 Feb;10(2):140-7. doi: 10.1006/cyto.1997.0268.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism
  • Biological Assay / standards
  • Cytokines / pharmacology
  • Female
  • Humans
  • Interleukin-10 / metabolism*
  • Interleukin-12 / metabolism*
  • Interleukin-4 / metabolism
  • Interleukin-6 / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Lupus Erythematosus, Systemic / metabolism*
  • Monocytes / metabolism*
  • Neutralization Tests


  • Cytokines
  • Interleukin-6
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4