Interleukin-10 response abnormalities in systemic lupus erythematosus

Scand J Immunol. 1997 Oct;46(4):406-12. doi: 10.1046/j.1365-3083.1997.d01-140.x.

Abstract

It has been previously reported that the production of interleukin-6 (IL-6) is often enhanced in systemic lupus erythematosus (SLE). The authors examined the secretion of IL-6, tumour necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor, IL-1 alpha and IL-4 by B cells and monocytes from lupus patients and compared this to the production in normal controls and in rheumatoid arthritis patients. IL-6 production was increased an average of 3.4-fold compared to that in normal subjects and 8.4-fold compared to rheumatoid arthritis patients. In SLE, a strongly positive correlation was found between the levels of IL-6 and TNF-alpha (R = 0.8987, P = 0.002). Since production of both IL-6 and TNF-alpha is regulated by IL-10, the enhancement of the production of these cytokines could reflect a defect in either IL-10 production or responsiveness. However, spontaneous production of IL-10 was enhanced in cultures of B cells and monocytes from lupus patients, compared to normal controls, the levels being increased 3.1- to 6-fold for monocytes and B cells, respectively. The finding of increased secretion of these cytokines implies an abnormality in IL-10-mediated suppression in SLE. To assess this possibility, the authors examined recombinant human IL-10-mediated suppression of IL-6 production by monocytes and B cells from lupus patients, compared to normal controls, and found that whereas IL-10 caused a concentration-dependent suppression of IL-6 production in normal B cells and monocytes, this suppression was deficient in B cells and monocytes from lupus patients. In SLE, it therefore appears that there may be an intrinsic defect in IL-10-induced suppression of cytokine synthesis. This could explain the increased levels of IL-10 and IL-6 found in this condition, and may also be responsible for the characteristic polyclonal B-cell activation that is seen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cells, Cultured
  • Humans
  • Immune Tolerance / drug effects
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / blood
  • Interleukin-10 / pharmacology
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / blood
  • Lipopolysaccharides / pharmacology
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Activation / drug effects
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism

Substances

  • Interleukin-6
  • Lipopolysaccharides
  • Interleukin-10