IL-1 Family Proteins

The interleukin 1 (IL-1) family is a group that consists of 11 cytokines that plays an essential role in the regulation of immune and inflammatory response to infections. The IL-1 family contains 7 members with agonistic functions (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β and IL-36γ). These members are involved in binding to a primary receptor subunit such as IL-1 RI/ IL-1 R1, which then triggers the recruitment of an accessory receptor to form the active receptor complex. Once these members activate the receptor complex, they activate MAPKs and NF-kappa B which stimulates the expression of pro-inflammatory cytokines, chemokines and secondary mediators of the inflammatory response. This thereby initiates an inflammatory immune response to infection.

Interleukin-1 alpha (IL-1α) also called hematopoietin 1 is an important member of the IL-1 family and is mainly produced by epithelial cells. It is essential for the initiation of inflammation, and the stimulation of fever and sepsis. In the initiation of inflammation, it induces the proliferation of CD4+ T cells and co-stimulates the production of CD8+ T cells, it stimulates the production of the cytokine, IL-2 and induces clonal expansion of mature B-cells and antibody secretion. Additionally, it increases the quantity of circulating blood neutrophils.

Interleukin-1 beta (IL-1β) also known as lymphocyte activating factor plays a similar role to IL-1α. It plays a critical role in regulating the inflammatory response. In order to execute its functions, the IL-1β precursor must be cleaved by cytosolic caspase 1 to form the mature IL-1β. This occurs via the activation of an inflammasome complex, which are multimeric proteins required for the activation of inflammation. This member of the IL-1 family is produced predominantly by activated macrophages. This cytokine is involved in a variety of cellular processes such as cell proliferation, cell differentiation and apoptosis.  

Interleukin-18 (IL-18) also known as interferon-gamma inducing factor is pro-inflammatory cytokine belonging to the IL-1 family of proteins. IL-18 is predominantly expressed by intestinal epithelial cells, keratinocytes and endothelial cells. IL-18 is involved in the modulation of both innate and adaptive immunity. IL-18 works in tandem with the cytokine IL-12 to carry out several functions including cell-mediated immunity after infection with microbial products such as lipopolysaccharide (LPS) produced by gram-negative bacteria. Additionally, IL-18 with the aid of IL-12 stimulates CD4+, CD8+ T cells and NK cells to secrete the pro-inflammatory cytokine IFNγ.

The IL-1 family also contains 4 members with antagonistic functions (IL-1Ra, IL-36Ra, IL-37 and IL-38). These members modulate a variety of pro-inflammatory responses of IL-1 and are secreted by a variety of cell types including epithelial cells, macrophages, dendritic cells, endothelial cells and B cells. IL-1Ra is the natural antagonist that blocks IL-1α and IL-1β activity. Likewise, IL-36Ra is the receptor antagonist for the pro-inflammatory cytokines IL-36α and IL-36β. It acts as a non-specific inhibitor of inflammation and innate immunity. As a whole, IL-1 family members with antagonistic functions inhibit inflammation by blocking IL-1 receptors thereby preventing signal transduction and reducing the pro-inflammatory response. ELISA Genie provides an extensive range of IL-1 ELISA kits that measure IL-1 ligands, signalling molecules and receptors.

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