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Immune complex-mediated cytokine production is regulated by classical complement activation both in vivo and in vitro

Johan Rönnelid1, Erik Ahlin, Bo Nilsson

  • 1Unit of Clinical Immunology, Uppsala University, Uppsala, Sweden. johan.ronnelid@klinimm.uu.se

Advances in Experimental Medicine and Biology
|November 26, 2008
PubMed

Insights

Immune complexes (IC) stimulate cytokine production, but results depend on complement cascade activity. In vitro studies require controlled complement pathways, while in vivo findings need context of complement function and specific autoantibodies like anti-SSA.

Area of Science:

  • Immunology
  • Cellular Biology
  • Autoimmunity

Background:

  • Immune complexes (IC) are crucial in immune responses, modulating cytokine production by various immune cells.
  • The classical complement cascade significantly influences IC-mediated cytokine induction in vitro.
  • Previous studies highlighted the role of complement in IC-induced cytokine profiles.

Purpose of the Study:

  • To investigate the influence of the classical complement cascade on IC-induced cytokine production in vitro.
  • To determine the factors affecting circulating IC levels and cytokine production in systemic lupus erythematosus (SLE).
  • To clarify the impact of in vivo complement activation and autoantibodies on IC-mediated responses.

Main Methods:

  • Stimulation of immune cells (monocytes, macrophages, plasmacytoid dendritic cells) with artificial IC and purified cryoglobulins.
  • Analysis of cytokine production in response to IC under varying complement conditions.
  • Evaluation of IC and cytokine levels in SLE patients, correlating with complement function and autoantibody presence (anti-SSA, anti-dsDNA).

Main Results:

  • The composition of cytokines induced by IC in vitro is significantly affected by the availability of an intact classical complement cascade.
  • In SLE, circulating IC levels and induced cytokine amounts depend on in vivo classical complement function.
  • The presence of anti-SSA autoantibodies correlated with IC and cytokine levels in SLE, unlike anti-dsDNA antibodies.

Conclusions:

  • Stringent control of the classical complement pathway during cell culture is essential for reproducible in vitro studies of IC-induced cytokine production.
  • In vivo interpretation of IC-related cytokine responses must consider both complement activation status and the presence of specific autoantibodies, particularly anti-SSA.
  • These findings underscore the complex interplay between complement, autoantibodies, and cytokine networks in autoimmune diseases.

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