Immunological and Inflammatory Functions of the Interleukin-1 Family

Abstract

More than any other cytokine family, the interleukin (IL)-1 family is closely linked to the innate immune response. This linkage became evident upon the discovery that the cytoplasmic domain of the IL-1 receptor type I is highly homologous to the cytoplasmic domains of all Toll-like receptors (TLRs). Thus, fundamental inflammatory responses such as the induction of cyclooxygenase type 2, increased expression of adhesion molecules, or synthesis of nitric oxide are indistinguishable responses of both IL-1 and TLR ligands. Both families nonspecifically affect antigen recognition and lymphocyte function. IL-1beta is the most studied member of the IL-1 family because of its role in mediating autoinflammatory diseases. Although the TLR and IL-1 families evolved to assist in host defense against infection, unlike the TLR family, the IL-1 family also includes members that suppress inflammation, both specifically within the IL-1 family but also nonspecifically for TLR ligands and the innate immune response.

Interleukin-1β Inhibition Prevents Choroidal Neovascularization and Does Not Exacerbate Photoreceptor Degeneration

“…1 Vascular endothelium, which constitutively expresses IL-1RI, 17 releases IL-6 17 and microparticles 18 on IL-1␤ stimulation. We show that collagen IV-expressing vascular endothelial cells in CNV express IL-1RI in vivo (Figure 3).…”

“…1 It induces angiogenesis in the cornea in vivo, 3 IL-6 expression, 17 and microparticle release from vascular endothelial cells in vitro. 18 IL-1RI is expressed on numerous cell types; notably, it is constitutively expressed on vascular endothelium.…”

“…1 IL-1␤ interacts with IL-1 receptor I (IL-1RI), composed of IL-1R and IL-1R accessory protein subunits. IL-1 receptor antagonist (IL1Ra) competes with IL-1␤ for its binding site.…”

“…IL-1 receptor antagonist (IL1Ra) competes with IL-1␤ for its binding site. 1 IL-1␤ is a potent inflammatory mediator with chemotactic 2 and angiogenic 3,4 properties. It is a neurotoxic mediator in ischemic brain injury 5 but can attenuate glutamate neurotoxicity in the retina 6 and protect against light-induced or hereditary photoreceptor degeneration.…”

The polypeptide biophysics of proline/alanine‐rich sequences (PAS): Recombinant biopolymers with PEG‐like properties

“…Here, we report on the extensive characterization of the hydrodynamic and biophysical properties of various PAS polymers and their comparison to PEG of different lengths. To this end, we have prepared the PAS polypeptides both as isolated biopolymer substances and as fusion proteins with IL‐1Ra, an approved biological drug (anakinra) that antagonizes interleukin‐1β 17. While showing prospects for the treatment of several autoinflammatory syndromes, e.g.…”