Immunomodulatory properties of human serum immunoglobulin A: anti-inflammatory and pro-inflammatory activities in human monocytes and peripheral blood mononuclear cells

Clin Exp Immunol. 2005 Jun;140(3):478-90. doi: 10.1111/j.1365-2249.2005.02779.x.


Our study investigated the immunomodulatory activities of human plasma-derived serum immunoglobulin (Ig)A. Previous findings seem contradictory indicating either pro- or anti-inflammatory activities. We used serum IgA purified from large plasma pools and studied the modulation of the release of cytokines and chemokines from resting and lipopolysaccharide (LPS, endotoxin)-stimulated human adherent monocytes and human peripheral blood mononuclear cells (PBMC). Our results indicate that IgA down-modulates the release of the pro-inflammatory chemokines monocyte chemoattractant protein (MCP) 1, macrophage inflammatory protein (MIP) 1alpha and MIP1beta from LPS-stimulated PBMC and the release of MCP1, MIP1alpha and MIP1beta from LPS-stimulated monocytes. Furthermore, we confirmed previous reports that plasma-derived serum IgA down-modulates the release of the pro-inflammatory cytokines, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, from LPS-stimulated monocytes and PBMC, and up-regulates the release of IL-1 receptor antagonist (IL-1RA) from resting and LPS-stimulated monocytes and resting PBMC. This IgA-mediated up-regulation of IL-1RA is independent of the simultaneous up-regulation of IL-1beta release, as shown by blocking the biological activity of IL-1beta with a neutralizing antibody. On the other hand, we also found an IgA-induced pro-inflammatory activity, namely IgA-mediated up-regulation of the release of pro-inflammatory IL-1beta as well as down-regulation of the anti-inflammatory cytokines IL-10 and IL-12p40 from LPS-stimulated monocytes and PBMC and a down-regulation of transforming growth factor (TGF)-beta from resting and LPS-stimulated PBMC. We conclude that human serum IgA has both an anti-inflammatory and a pro-inflammatory capacity and this dual capacity might contribute to the feedback mechanisms maintaining a balance between pro-inflammatory and anti-inflammatory activities.

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2 / immunology
  • Chemokine CCL3
  • Chemokine CCL4
  • Cytokines / immunology*
  • Down-Regulation / immunology
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology*
  • Interleukin-1 / immunology
  • Interleukin-10 / immunology
  • Interleukin-12 / immunology
  • Interleukin-6 / immunology
  • Leukocytes, Mononuclear / immunology*
  • Lipopolysaccharides / immunology
  • Macrophage Inflammatory Proteins / immunology
  • Monocytes / immunology
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Transforming Growth Factor beta / immunology
  • Tumor Necrosis Factor-alpha / immunology
  • Up-Regulation / immunology


  • CCL2 protein, human
  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Cytokines
  • Immunoglobulin A
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • Macrophage Inflammatory Proteins
  • Receptors, Interleukin-1
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12