Selective Suppression of IL-12 Production by Chemoattractants

• Published in: The Journal of immunology (1950) Vol. 164; no. 6; pp. 3009 - 3017
• Main Authors: Braun, Michael C, Lahey, Edward, Kelsall, Brian L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.03.2000
• Subjects: Cells, Cultured; Chemokine CCL2 - pharmacology; Chemokine CCL7; Chemokine CCL8; Complement C5a - pharmacology; complement component C5a; Cytokines; Dendritic Cells - immunology; Dendritic Cells - metabolism; eotaxin; g-Interferon; Humans; Immunosuppressive Agents - pharmacology; Interleukin-10 - physiology; Interleukin-12 - antagonists & inhibitors; Interleukin-12 - biosynthesis; Interleukin-12 - genetics; macrophage chemoattractant protein; macrophage inflammatory protein 1^a; Monocyte Chemoattractant Proteins - pharmacology; Monocytes - immunology; Monocytes - metabolism; RANTES; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - metabolism; stromal cell-derived factor 1; Virulence Factors, Bordetella - pharmacology
• ISSN: 0022-1767; 1550-6606
• 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.