Intravenous immunoglobulin skews macrophages to an anti-inflammatory, IL-10-producing activation state

• DOI: 10.1189/jlb.3vma0315-078r
• Publication Date: 2015-07-28T01:41:09Z
• Authors: Lisa K Kozicky; Zheng Yu Zhao; Susan C Menzies; Mario Fidanza; Gregor S D Reid; Kevin Wilhelmsen; Judith Hellman; Naomi Hotte; Karen L Madsen; Laura M Sly
• Keywords: Proinflammatory cytokine

Abstract Intravenous Ig is used to treat autoimmune or autoinflammatory disorders, but the mechanism by which it exerts its immunosuppressive activity not understood completely. To examine impact of intravenous on macrophages, we compared cytokine production LPS-activated macrophages in presence and absence Ig. treatment induced robust IL-10 response LPS, relative LPS stimulation alone, reduced proinflammatory cytokines. This anti-inflammatory, Ig-induced activation was sustained for 24 h could only be if were provided within 1 stimulation. led enhanced prolonged MAPKs, Erk1/2, p38, Erk5, inhibition each suppression IL-12/23p40. occurred rapidly + sufficient reduce IL-12/23p40 LPS. induction transcriptionally regulated. played a direct role reducing treated with as from mice deficient IL-10R β chain compromised their ability production. Finally, intraperitoneal injection into activated produce high levels during subsequent concurrent challenge, respectively. These findings identify key anti-inflammatory mediator produced Ig-treated provide insight novel may dampen down inflammatory responses patients diseases.