Interleukin-6 inhibition in the treatment of autoinflammatory diseases

Abstract

Autoinflammatory diseases are characterized by abnormalities that prevent innate immune cells from producing autoantibodies. While interleukin (IL)-6 is not directly associated with inflammasomes, like IL-1β or IL-18, it plays an important role in the pathogenesis of autoinflammatory diseases. Studies of autoinflammatory diseases, such as familial Mediterranean fever, cryopyrin-associated periodic syndrome, and tumor necrosis factor receptor-associated periodic syndrome, have shown IL-6 to be a promising therapeutic target. It has also been suggested that inhibition of IL-6 may have a therapeutic effect on amyloidosis, which is frequently associated with these chronic inflammatory diseases. In this study, we discuss the most recent research on the role of IL-6 in autoinflammatory diseases and its potential as a therapeutic target in their treatment.

Keywords: amyloidosis; autoinflammatory diseases; familial mediterranean fever; inflammasome; interleukin-6.

Figure 1

Cellular signals associated with inflammasome activation and proteins affected by autoinflammatory disease-related gene variants. ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; CAPS, cryopyrin-associated periodic syndrome; DAMPs, damage-associated molecular patterns; FMF, familial Mediterranean fever; IL, interleukin; IL-1R, interleukin-1 beta receptor; NLRP3, nucleotide-binding oligomerization domain-like receptor protein 3; PAMPs, pathogen-associated molecular patterns; SAA, serum amyloid A; TNF, tumor necrosis factor; TNFR, tumor necrosis factor receptor; TRAPS, TNF receptor-associated periodic syndrome.

Figure 2

The cytokine network in familial Mediterranean fever. CXCL10: interferon gamma-inducible protein 10, G-CSF, granulocyte-colony stimulating factor; ICAM-1, intercellular adhesion molecule 1; IFN-γ, interferon-γ; IL, interleukin; TNF, tumor necrosis factor.