Serum Interleukin 6 Levels May Predict Presentation of IgG4-Related Disease

Interleukin (IL) 6 plays multiple roles in immune response, including promoting the activation and differentiation of T cells and B cells. The presence of IL-6 is also associated with some rheumatic diseases. Examples: The hyperproduction of IL-6 in lymphoid tissue causes multicentric Castleman’s disease (MCD), a polyclonal lymphoproliferative disorder associated with hepatomegaly and/or splenomegaly. Rheumatologists have found patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) tend to have numerous immunopositive cells for IL-6 in their affected organs. Additionally, research has shown some patients with IgG4-related disease (IgG4-RD) have clinical and histopathological presentations similar to those of patients with MCD and AAV, although patients with IgG4-RD rarely present with swelling of the liver and spleen.

Recent research suggests serum IL-6 levels at the onset of IgG4-RD correlate with clinical inflammatory parameters, such as serum levels of C-reactive protein (CRP), hemoglobin and albumin. However, the significant correlation between IL-6 level and IgG4 level is unknown. The research by Satoshi Tsukuda, PhD, assistant professor of gastroenterology and hepatology at the Kansai Medical University, Japan, and colleagues indicates serum IL-6 may be associated with involvement of the bile duct, liver and spleen. This association between splenic enlargement and higher serum IL-6 occurs even in the absence of cirrhosis and extrahepatic obstruction of the portal vein. The investigators published their findings online Jan. 17 in PLoS One.¹

The retrospective study included 43 patients with IgG4-RD who were diagnosed in accordance with the current criteria. The cohort included a heterogeneous group of patients with multiple underlying pathogenic components. The affected organs associated with IgG4-RD were the lacrimal gland (4%), salivary gland (37%), pancreas (86%), biliary tract (63%), liver (9%), spleen (16%), kidney (19%), retroperitoneum (9%), lymph node (49%) and aorta (2%). The researchers reported a median serum IL-6 level of 2.2 pg/mL, a median CRP level of 0.10 mg/dL and a median IgG4 level of 290 mg/dL.

The investigators divided the patients into two groups using an IL-6 cut-off of 4 pg/mL. They found the high IL-6 group (n=10) was older, had lower albumin and had higher CRP and higher aspartate aminotransferase (AST) than the low IL-6 group (n=33). Although the low IL-6 group had significantly more salivary gland involvement (46%) than the high IL-6 group (10%), there was significantly more hepatic swelling, kidney swelling and splenomegaly in the high IL-6 group compared with the low IL-6 group (liver: 40% vs. 0%; kidney: 40% vs. 12%; spleen 40% vs. 9%). Also, biliary tract involvement was more common in the high IL-6 group (90% vs. 58%), but the difference was not statistically significant.

When the researchers evaluated the ability of serum IL-6 to predict relapse, they found—unlike serum IgG4, which can be used to predict IgG4-RD relapse—no significant differences in the median observation periods and IL-6 levels between relapse and non-relapse groups.

Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

Reference

1. Tsukuda S, Ikeura T, Ito T, et al. Clinical implications of elevated serum interleukin-6 in IgG4-related disease. PLoS One. 2020 Jan 17;15(1):e0227479. eCollection 2020.