Treatment with high-dose intravenous immunoglobulin (IVIG) has been used to reduce the debilitating effects of inflammation associated with arthritis and other autoimmune diseases. This treatment consists of a highly purified group of antibodies called immunoglobulin G (IgG). Previous work has shown that the anti-inflammatory activity of IVIG is linked to a sugar-containing molecule, sFc, found in a subset of IgG antibodies. The sFc molecule targets certain immune cells, including dendritic cells and macrophages, by binding to a molecule on these cells known as DC-SIGN.
To further understand how IVIG can limit inflammation, NIAID-funded investigators used mice that were genetically engineered to produce human DC-SIGN (hDC-SIGN). These mice were protected from experimental inflammatory arthritis by IVIG. When the researchers treated the mice with sFc, the animals produced interleukin-33 (IL-33), an immune-system molecule that contributes to an anti-inflammatory environment.
The production of IL-33, in turn, led to increased numbers of basophils, immune cells that further promote the response by producing the anti-inflammatory molecule IL-4. The basophils also increased the levels of FcγRIIB, a molecule that dampens the inflammatory response caused by macrophages. Symptoms of arthritic inflammation were suppressed in mice treated with IL-33, IL-4, or basophils treated with IL-33.
This newly discovered pathway explains how IVIG can produce an anti-inflammatory response in arthritis and may lead to the development of new treatments for autoimmune diseases.
Reference: Anthony RM, Kobayashi T, Wermeling F, Ravetch JV. Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature. 2011 Jun 19;475(7354):110-3.
Last Updated January 07, 2013
Last Reviewed January 07, 2013