Send to

Choose Destination
Cytokine. 2018 Feb;102:145-148. doi: 10.1016/j.cyto.2017.08.001. Epub 2017 Aug 18.

IL-1 family cytokines and receptors in IgG4-related disease.

Author information

Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.
Institute of Protein Biochemistry, National Research Council, Naples, Italy.
Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy. Electronic address:



The IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect almost any organ, often associated with eosinophilia and increased levels of IgE and IgG4. Overexpression in tissues of Th2-related cytokines but also of IFN-γ has been reported. Given the major role of Il-1 family cytokines in inducing and regulating inflammation, and the paucity of data so far available in IgG-RD, we performed a comprehensive analysis of IL-18, related IL-1 family cytokines and soluble receptors in these patients.


Fifteen patients fulfilling the criteria for the diagnosis of IgG4-RD and 80 blood donors as control were recruited. Cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, ST2/sIL-1R4) and antagonists (IL-1Ra, IL-18 binding protein -IL-18BP-) were measured in sera by multiarray ELISA assay. Free IL-18 was calculated as the amount of IL-18 not inhibited by IL-18BP.


Half of the patients had a multiorgan disease, mainly affecting retroperitoneum, lymph nodes and pancreas. sIL-1R1 (p=0.0001), sIL-1R2 (p=0.0024), ST2/sIL-1R4 (p=0.002) were significantly increased in IgG4-RD sera compared with healthy controls; sIL-R3 was significantly lower in patients vs controls (p=0,0006).


The increased levels of the soluble forms of the two IL-1 receptors IL-1R1 and IL-1R2 suggest the need to dampen IL-1-mediated inflammation at the tissue level. Elevated circulating ST2/sIL-1R4 levels may represent the marker of an ongoing protective mechanism, but their contribution to organ damage cannot be excluded. On the whole, the data suggest a tight control of IL-1 family cytokines signalling in IgG4-RD.


IL-1 family; IL-18; IgG4-related disease; ST2/IL-1R4


Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center