Cytokine Regulation in Immune Responses
Summary
Cytokines are central mediators of immune communication, orchestrating the activation, differentiation and resolution of both innate and adaptive responses. Precise regulation of cytokine production and signalling is essential to mount protective immunity against pathogens while preventing excessive inflammation and tissue damage. Interleukin-18 (IL-18), a member of the IL-1 family, exemplifies this balance by driving interferon-γ production in natural killer cells and T lymphocytes, yet requiring tight control by its natural inhibitor, IL-18 binding protein (IL-18BP), to avert chronic inflammation. Activation of cytosolic multiprotein inflammasomes governs the maturation and release of IL-18 and related cytokines, linking pathogen or damage sensing to downstream effector functions. Dysregulated cytokine networks underlie a spectrum of disorders from autoimmune diseases to metabolic syndrome, and are implicated in fibrosis, organ injury and cancer. Recent advances in structural biology, biomarker profiling and therapeutic blockade have illuminated the molecular checkpoints that fine-tune cytokine bioactivity, opening avenues for targeted intervention in inflammatory and immune-mediated diseases.
Research from Nature Portfolio
Recent studies have resolved high-resolution crystal structures of IL-18 in complex with its receptor chains, revealing a unique arrangement of receptor domains that distinguishes IL-18 signalling from other IL-1 family members. Detailed mapping of binding hotspots and receptor interfaces has clarified how conformational changes initiate intracellular signalling and highlighted allosteric sites amenable to modulation. These structural insights provide a blueprint for the rational design of novel antagonists and biologics aimed at selectively dampening IL-18-driven inflammation without broadly suppressing host defence.
Cytokine Regulation in Immune Responses publication trend
The graph below shows the total number of articles in cytokine regulation in immune responses across all publications each year (not limited to Nature Index journals).
Technical terms
Cytokine: A small secreted protein that mediates intercellular communication in the immune system.
Interleukin-18 (IL-18): A proinflammatory cytokine of the IL-1 family that drives interferon-γ production and modulates both innate and adaptive immunity.
Inflammasome: A cytosolic multiprotein complex that activates caspase-1, leading to processing and release of proinflammatory cytokines such as IL-1β and IL-18.
IL-18 binding protein (IL-18BP): A naturally occurring inhibitor that sequesters IL-18, reducing its bioavailability and dampening inflammatory signalling.
Receptor: A cell-surface protein that specifically recognises and binds a cytokine to initiate downstream signalling cascades.
References
- Disruption of IL-18 signaling via engineered IL-18BP biologics alleviates experimental cholestatic liver disease. Biomedicine & Pharmacotherapy (2023).
- Interleukin-18 in Health and Disease. International Journal of Molecular Sciences (2019).
- IL-1β/IL-6/CRP and IL-18/ferritin: Distinct Inflammatory Programs in Infections. PLOS Pathogens (2016).
- The structural basis for receptor recognition of human interleukin-18. Nature Communications (2014).
- Distinct Licensing of IL-18 and IL-1β Secretion in Response to NLRP3 Inflammasome Activation. PLOS ONE (2012).
- Interleukin-18 and IL-18 Binding Protein. Frontiers in Immunology (2013).
- Unique Action of Interleukin-18 on T Cells and Other Immune Cells. Frontiers in Immunology (2018).
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