Selective suppression of IL-12 production by chemoattractants

J Immunol. 2000 Mar 15;164(6):3009-17. doi: 10.4049/jimmunol.164.6.3009.


We investigated the ability of chemoattractants to affect IL-12 production by human monocytes and dendritic cells. We found that pretreatment of monocytes with macrophage chemoattractant proteins (MCP-1 to -4), or C5a, but not stromal-derived factor-1, macrophage inflammatory protein-1alpha, RANTES, or eotaxin, inhibited IL-12 p70 production in response to stimulation with Staphylococcus aureus, Cowan strain 1 (SAC), and IFN-gamma. The production of TNF-alpha and IL-10, however, was minimally affected by any of the chemoattractants. The degree of inhibition of IL-12 p70 production by MCP-1 to -4 was donor dependent and was affected by the autocrine inhibitory effects of IL-10. In contrast, C5a profoundly suppressed IL-12 production in an IL-10-independent fashion. Neither TGF-beta1 nor PGE2 was important for the suppression of IL-12 by any of the chemoattractants tested. The accumulation of mRNA for both IL-12 p35 and p40 genes was inhibited by chemokine pretreatment. Interestingly, MCP-1 to -4 and C5a did not suppress IL-12 production by monocyte-derived dendritic cells (DC) stimulated with CD40 ligand and IFN-gamma or by SAC and IFN-gamma, suggesting that these factors may act at the site of inflammation to suppress IL-12 and IFN-gamma production rather than in the lymph node to affect T cell priming. Despite the inability of C5a to inhibit IL-12 production by DCs, the receptor for C5a (CD88) was expressed by these cells, and recombinant C5a induced a Ca2+ flux. Taken together, these results define a range of chemoattractant molecules with the ability to suppress IL-12 production by human monocytes and have broad implications for the regulation of immune responses in vivo.

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2 / pharmacology
  • Chemokine CCL7
  • Chemokine CCL8
  • Complement C5a / pharmacology
  • Cytokines*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-10 / physiology
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / genetics
  • Monocyte Chemoattractant Proteins / pharmacology*
  • Monocytes / immunology
  • Monocytes / metabolism
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • Virulence Factors, Bordetella / pharmacology


  • CCL13 protein, human
  • CCL7 protein, human
  • CCL8 protein, human
  • Chemokine CCL2
  • Chemokine CCL7
  • Chemokine CCL8
  • Cytokines
  • Immunosuppressive Agents
  • Monocyte Chemoattractant Proteins
  • RNA, Messenger
  • Virulence Factors, Bordetella
  • Interleukin-10
  • Interleukin-12
  • Complement C5a