The interleukin-1 family

The interleukin-1 family: a central mediator of innate immunity and inflammation

Interleukins (ILs) are a group of cytokines produced by leukocytes and non-immune cells such as fibroblasts, endothelial, epithelial, smooth muscle, and bone marrow cells[1]. Often called immunological ‘secondary messengers’, ILs mainly act as immunomodulators. They also aid in cell proliferation, differentiation, activation, migration, and adhesion. There are about 40 different types of Ils. Interleukin-1 (IL-1) cytokines were the first discovered and are also the most extensively studied among ILs [1,2]. IL-1 have had a broad impact in immunology and medicine at large.

The IL-1 family of cytokines

IL-1 belongs to the specific class of interleukins that are often known for their pro- and anti-inflammatory cytokine members. From the initial discovery of two members, IL-1α and IL-1β [3], the family of IL-1 has expanded to include nine more cytokines, IL-1Ra, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37, and IL-38 [4]. Among these 11 cytokines, seven of them have agonist activity (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ), three are receptor antagonists (IL-1Ra, IL-36Ra, IL-38), and one is an anti-inflammatory cytokine (IL-37) [4,5]. Each IL-1 cytokines activate intracellular signalling by binding to specific receptors and sometimes co-receptors. There are ten types of IL-1 receptors that include cytokine-specific receptors, co-receptors, and inhibitory receptors. Among them, six are receptor chains forming four signalling receptor complexes, two are decoy receptors (IL-1R2, IL-18R), and two are negative regulators (SIGIRR, IL-1RAcP) [4,5]. Most IL-1 receptors have a similar structure containing three extracellular immunoglobulin (Ig) domains and an intracellular Toll-like/IL-1R (TIR) domain. Below is a list of the IL-1 family of cytokines with specific receptors and co-receptors. Sino Biological has developed superior reagents and products that range from recombinant proteins, antibodies, ELISA kits, and more. These products could help accelerate research on the IL-1 family of cytokines as well as other ILs.

List of IL-1 family members and receptors

IL-1 signalling and associated diseases

The protein production, maturation, receptor binding, and signalling of the IL-1 family of cytokines are tightly controlled [5]. For example, the 271 and 269 amino acid residue precursors of IL-1α and IL-1β are cleaved into mature forms by calpain and caspase-1 activated in the inflammasome, respectively [6,7]. Similarly, IL-1s have a defined specificity while binding to receptors, as listed in the table [6,8]. The binding of IL-1s to specific IL-1 receptors leads to downstream events and signal transduction, eliciting an inflammation [6,7,9] (Figure 1). However, loss of homeostasis leads to various pathological conditions. Even though the primary role of IL-1 family members is considered to be in immune regulation, its scope is beyond inflammatory diseases. The IL-1 family of cytokines is implicated in multiple pathologies [6], such as autoimmune diseases [10], cancer progression [11], neurodegeneration [12], cardiovascular diseases [13], and infectious diseases like COVID-19 [14].

IL-1 family cytokines as drug targets and anti-IL-1 therapy  

IL-1 family of cytokines is one of the most popular targets in the treatment of multiple pathologies [6, 10-14]. Anakinra is a clinically approved recombinant IL-1Ra that helps block the activity of IL-1α and IL-1β [4]. It has been used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, macrophage-activating syndrome (MAS), metastatic colon cancer, and many other conditions. Canakinumab and Gevokizumab are monoclonal antibodies against IL-1β that are used in the treatment of multiple conditions such as Adult-onset Still’s disease (AOSD), lung cancer, and auto-inflammatory diseases [15]. MABp1 is an anti-IL-1α therapeutic antibody that has been used in the treatment of advanced colorectal cancer. Rilonacept is a dimeric fusion protein consisting of portions of the IL-1R1 and the IL-1RAcP linked to the Fc domain of IgG1. It is used to treat recurrent Pericarditis and chronic inflammatory disorders [16]. Anti-IL-1 therapy has become an attractive modality for the treatment of many diseases.

Featured recombinant IL-1 family proteins

Recombinant IL-1β protein

Sino Biological has developed bioactive recombinant IL-1β cytokines from various species, such as human, mouse, rabbit, rat, rhesus, feline, and canine. Compared to a competing product, Sino Biological's IL-1β protein demonstrates a higher bioactivity.

Recombinant IL-18 proteins

Sino Biological has developed high bioactivity IL-18 proteins from multiple species. The activity of these proteins has been validated in IFN-γ induction experiments and binding assays against the IL-18 receptors.


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11.       Zhang, W., Borcherding, N., & Kolb, R. (2020). IL-1 Signaling in Tumor Microenvironment. Advances in experimental medicine and biology, 1240, 1–23.

12.       Voet, S., Srinivasan, S., Lamkanfi, M., & van Loo, G. (2019). Inflammasomes in neuroinflammatory and neurodegenerative diseases. EMBO molecular medicine, 11(6), e10248.

13.       Abbate, A., Toldo, S., Marchetti, C., Kron, J., Van Tassell, B. W., & Dinarello, C. A. (2020). Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease. Circulation research, 126(9), 1260–1280.

14.       Mardi, A., Meidaninikjeh, S., Nikfarjam, S., Majidi Zolbanin, N., & Jafari, R. (2021). Interleukin-1 in COVID-19 Infection: Immunopathogenesis and Possible Therapeutic Perspective. Viral immunology, 34(10), 679–688.

15.       Blech, M., Peter, D., Fischer, P., Bauer, M. M., Hafner, M., Zeeb, M., & Nar, H. (2013). One target-two different binding modes: structural insights into gevokizumab and canakinumab interactions to interleukin-1β. Journal of molecular biology, 425(1), 94–111.

16.       Stahl, N., Radin, A., & Mellis, S. (2009). Rilonacept--CAPS and beyond. Annals of the New York Academy of Sciences, 1182, 124–134.


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