title: C5a suppresses the production of IL-12 by IFN-gamma-primed and lipopolysaccharide-challenged human monocytes.
abstract: IL-12 is a key mediator of the immune response, skewing T lymphocytes toward a type 1 cytokine pattern. Priming with IFN-gamma or GM-CSF is required for expression of IL-12p70 by cells in which IL-12 is inducible by bacterial products such as LPS. We here show for the first time that the production of bioactive IL-12 by human monocytes can be significantly suppressed by C5a if applied to IFN-gamma-primed monocytes before LPS stimulation. There was a dose-dependent suppression by IL-12 (p70) on the levels of intracellular cytokine production and cytokine secretion. mRNA studies consistently showed a reduction of IL-12p40 and IL-12p35 expression by stimulation in the presence of C5a. The results of several different experimental approaches suggest that IL-12 down-regulation was not due to endogenous IL-10, IL-4, or PGE2 production induced by C5a. Moreover, stimulation of IFN-gamma-primed monocytes with C5a did not lead to a down-regulation of the CD14 Ag, which is an LPS receptor. These findings show that the anaphylatoxin C5a has the capacity to directly interact with the complex regulation of IL-12.
authors.affiliation: Department of Dermatology and Allergology, Hannover Medical University, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wittmann
authors.forename: J
authors.initials: J
authors.lastname: Zwirner
authors.forename: V A
authors.initials: VA
authors.lastname: Larsson
authors.forename: K
authors.initials: K
authors.lastname: Kirchhoff
authors.forename: G
authors.initials: G
authors.lastname: Begemann
authors.forename: A
authors.initials: A
authors.lastname: Kapp
authors.forename: O
authors.initials: O
authors.lastname: Götze
authors.forename: T
authors.initials: T
authors.lastname: Werfel
mesh_terms: D000276:Adjuvants, Immunologic / Q000096:biosynthesis; D002478:Cells, Cultured; D015936:Complement C5a / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D015936:Complement C5a; D007371:Interferon-gamma; D015232:Dinoprostone