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Immune complex size and complement regulate cytokine production by peripheral blood mononuclear cells

J N Jarvis1, C Xu, W Wang

  • 1Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma 73013, USA. james-jarvis@ouhsc.edu

Clinical Immunology (Orlando, Fla.)
|December 22, 1999
PubMed

Insights

Immune complex size and complement interaction influence inflammation. Larger immune complexes and those without complement activation induced greater inflammatory cytokine release in juvenile rheumatoid arthritis research.

Area of Science:

  • Immunology
  • Rheumatology
  • Cellular Biology

Background:

  • Immune complexes in juvenile rheumatoid arthritis (JRA) exhibit variable size, composition, and inflammatory potential.
  • Understanding the factors governing immune complex proinflammatory effects is crucial for JRA pathogenesis.

Purpose of the Study:

  • To elucidate the specific roles of size and composition in immune complex-mediated inflammation.
  • To investigate how complement influences the inflammatory capacity of immune complexes.

Main Methods:

  • Incubation of peripheral blood mononuclear cells (PBMCs) with distinct immune complex preparations (opsonized, unopsonized, complement-solubilized).
  • Enzyme-linked immunosorbent assay (ELISA) to quantify IL-1beta and IL-8 secretion.
  • Sucrose density gradient ultracentrifugation to assess immune complex size.
  • Complement component C4 binding assays.

Main Results:

  • Immune complexes formed with complement were less potent inducers of IL-1beta and IL-8 than unopsonized complexes.
  • Complement-solubilized immune precipitates demonstrated intermediate cytokine induction capacity.
  • Unopsonized complexes and solubilized precipitates were larger than opsonized complexes.
  • Fluid-phase C4 binding, without altering size, enhanced IL-1beta secretion.

Conclusions:

  • Complement significantly modulates the inflammatory response to immune complexes, partly through size regulation.
  • Immune complex size is a critical determinant of their capacity to stimulate leukocyte cytokine secretion.
  • Further research into complement's role in JRA immune complexes is warranted.

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