Different roles of interleukin 6 and interleukin 11 in the liver: implications for therapy

Figures & data

Figure 1. Number of publications for IL6 (gray) or IL11 (black) by year (1985–2019). The R package Pubmedwordcloud was used to generate these plots using case insensitive keywords ‘il6ʹ, ‘il-6ʹ, ‘interleukin-6ʹ, ‘interleukin 6ʹ for IL6 and ‘il-11ʹ, ‘interleukin-11ʹ and ‘interleukin 11ʹ for IL11

Figure 2. IL11RA is expressed on different cell types as compared to IL6R. Graphs showing example data for (a) correlated gene expression (COL1A1 vs COL1A2), (b) unrelated gene expression (COL1A1 vs GAPDH), and (c) IL11RA vs IL6R gene expression, which appears largely exclusive and in disparate cell types. The expression values are normalized counts obtained from the FANTOM consortium.¹⁷

Table 1. Overview of established and hypothetical uses of IL6 or IL11 therapies across organs and diseases

Approach	Molecule	Disease
IL6 trans gain-of-function	Hyper-IL6	Acute liver failure^Citation42,Citation44,Citation45* Partial hepatectomy^Citation43*
Inhibition of IL6 cis and trans signaling	Anti-IL6 or IL6R antibodies	Cancer (Prostate cancer, renal carcinoma, and multiple myeloma)^Citation64,Citation65# Castelman’s disease^Citation66 Cytokine storm syndrome^Citation67 Giant cell arteritis^Citation68 Neuromyelitis optica^Citation69# Rheumatoid arthritis^Citation51,Citation70,Citation71 Systemic juvenile idiopathic arthritis^Citation72 Takayasu arteritis^Citation73
Inhibition of IL6 trans-signaling only	Gp130 decoy constructs (e.g. soluble gp130)	IBD^Citation51#
Inhibition of IL11 signaling	Anti-IL11 or IL11RA antibodies	Acute liver failure^Citation8* Cardiorenal fibrosis^Citation5* Idiopathic pulmonary fibrosis^Citation9* Inflammatory bowel disease^Citation11* Metabolic liver disease^Citation10,Citation28* NASH^Citation10*

* pre-clinical study; ^# ongoing clinical trial.

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