Research Progress and Functional Overview of Interleukins

The IL-1 family contains 11 distinct members. Typical members such as IL-1, IL-18, IL-33 and IL-36 bind specifically to corresponding primary membrane receptors. Activation of IL-1α, IL-1β, IL-18, IL-33 and multiple IL-36 isoforms can trigger downstream MAPKK and NF-κB cascades, ultimately driving inflammatory reactions. Conversely, several other members of the IL-1 family exert anti-inflammatory biological effects. As a core pro-inflammatory cytokine, IL-1 participates in the co-stimulation of helper T cells, promotes the maturation and proliferation of B lymphocytes, activates NK cells, and serves as a key regulatory factor in the occurrence and development of inflammation.

IL-10 is a classic anti-inflammatory cytokine, mainly secreted by activated T lymphocytes, B cells, macrophages and mononuclear cells. It can regulate the cytokine secretion profile of macrophages, promote the activation of B cells and the differentiation of Th2 cells, while effectively suppressing the activation and cytokine release of Th1 cells. Endogenous IL-10 exists in the form of homodimer, which binds to the tetrameric heterodimeric IL-10 receptor complex, thereby blocking the transduction of IL-6, TNF and other pro-inflammatory signaling pathways. Current studies have confirmed that IL-10 is closely associated with the progression of non-small cell lung cancer.

The IL-12 family consists of four major members. As a branch of the IL-6 superfamily, IL-12, IL-25, IL-27 and IL-35 are unique heterodimeric cytokines. They activate the JAK/STAT signaling axis and induce the phosphorylation modification of STAT1/3/4 proteins to exert biological functions. IL-12 is essential for initiating and maintaining Th1-type cellular immunity, assisting the host in resisting invasion and infection by various intracellular pathogens.

The IL-17 family includes 6 ligands and 5 corresponding receptors, playing an indispensable role in innate and adaptive immune regulation. IL-17A is the signature molecule of this family, which defends the host against extracellular microbial infections and mediates excessive inflammatory damage in multiple autoimmune diseases; IL-17C shares similar biological properties with IL-17A. IL-17F mainly participates in mucosal immune defense, while IL-17E enhances Th2-type immune responses. The IL-17 family can activate downstream MAPK, NF-κB and C/EBPs signaling axes to induce the expression of antibacterial cytokines and chemokines, and the adaptor protein Act1 is recognized as the core transduction mediator in this pathway.