Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/15161
Título
IVIg Promote Cross-Tolerance against Inflammatory Stimuli In Vitro and In Vivo.
Autor(es)
Fecha de publicación
2018
Cita
J Immunol . 2018 Jul 1;201(1):41-52.
Idioma
Inglés
Tipo de documento
journal article
Resumen
IVIg is an approved therapy for immunodeficiency and for several autoimmune and inflammatory diseases. However, the molecular basis for the IVIg anti-inflammatory activity remains to be fully explained and cannot be extrapolated from studies on animal models of disease. We now report that IVIg impairs the generation of human monocyte-derived anti-inflammatory macrophages by inducing JNK activation and activin A production and limits proinflammatory macrophage differentiation by inhibiting GM-CSF-driven STAT5 activation. In vivo, IVIg provokes a rapid increase in peripheral blood activin A, CCL2, and IL-6 levels, an effect that can be recapitulated in vitro on human monocytes. On differentiating monocytes, IVIg promotes the acquisition of altered transcriptional and cytokine profiles, reduces TLR expression and signaling, and upregulates negative regulators of TLR-initiated intracellular signaling. In line with these effects, in vivo IVIg infusion induces a state tolerant toward subsequent stimuli that results in reduced inflammatory cytokine production after LPS challenge in human peripheral blood and significant protection from LPS-induced death in mice. Therefore, IVIg conditions human macrophages toward the acquisition of a state of cross-tolerance against inflammatory stimuli, an effect that correlates with the net anti-inflammatory action of IVIg in vivo.
MESH
Activins | Animals | Anti-Inflammatory Agents | Cells, Cultured | Chemokine CCL2 | Enzyme Activation | Granulocyte-Macrophage Colony-Stimulating Factor | Humans | Immune Tolerance | Immunoglobulins, Intravenous | Inflammation | Interleukin-6 | JNK Mitogen-Activated Protein Kinases | Lipopolysaccharides | Macrophages | Mice | Monocytes | STAT5 Transcription Factor
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