Interleukin-1 Family Cytokine Dynamics in Inflammatory Responses

The interleukin-1 (IL-1) family comprises a group of potent pro-inflammatory cytokines, including IL-1α, IL-1β, IL-18 and IL-33, that orchestrate both innate and adaptive immune responses. Members of this family act as early warning signals or “alarmins” on tissue damage or infection, triggering cascades of downstream mediators such as chemokines, adhesion molecules and other cytokines. Their activity is tightly regulated at multiple levels: precursor proteins often require proteolytic processing by proteases such as caspases and calpains; specialised multiprotein platforms known as inflammasomes sense danger signals and mediate cytokine maturation; and gasdermin family members form membrane pores to enable unconventional release of these mediators. Distinct modes of cell death—apoptosis, pyroptosis or necrosis—further influence which IL-1 species are released and how surrounding cells respond. Dysregulation of IL-1 dynamics underlies a wide spectrum of disorders, from autoimmune and autoinflammatory syndromes to sterile injury in the central nervous system and chronic lung disease. Advances in understanding the molecular switches that govern cytokine activation, release and receptor engagement are guiding the development of targeted therapies and diagnostic biomarkers with global relevance in infection, tissue repair and inflammatory pathology.

Research from Nature Portfolio

Recent studies have revealed that a subset of human T helper 17 (TH17) cells repurpose the gasdermin E pore–forming machinery, traditionally associated with pyroptotic cell death, to secrete IL-1α without loss of cell viability. Engagement of a T-cell-intrinsic NLRP3 inflammasome triggers a cascade of caspase-8, caspase-3 and gasdermin E cleavage, enabling rapid alarmin release upon antigen stimulation. This unconventional pathway broadens our understanding of how adaptive immune cells can deploy innate signalling modules and has significant implications for host defence against pathogens such as Candida albicans.

Interleukin-1 Family Cytokine Dynamics in Inflammatory Responses publication trend

The graph below shows the total number of articles in interleukin-1 family cytokine dynamics in inflammatory responses across all publications each year (not limited to Nature Index journals).

Technical terms

Interleukin-1α (IL-1α): A pro-inflammatory cytokine released as an alarmin upon cell injury or necrosis.

Interleukin-1β (IL-1β): A cytokine activated by proteolytic cleavage in inflammasomes and released to drive inflammation.

Inflammasome: A cytosolic multiprotein complex that senses danger signals and activates caspase-1 to process IL-1β and IL-18.

Pyroptosis: A lytic form of programmed cell death mediated by gasdermin pores, often accompanied by cytokine release.

Gasdermin: A family of pore-forming proteins that create membrane channels for unconventional cytokine secretion.

Damage‐associated molecular pattern (DAMP): Endogenous molecules released by stressed or dying cells that trigger sterile inflammation.

References

1. Human TH17 cells engage gasdermin E pores to release IL-1α on NLRP3 inflammasome activation. Nature Immunology (2023).
2. Constitutive DAMPs in CNS injury: From preclinical insights to clinical perspectives. Brain Behavior and Immunity (2024).
3. Gasdermin D membrane pores orchestrate IL-1α secretion from necrotic macrophages after NFS-rich silica exposure. Archives of Toxicology (2023).
4. Species-specific IL-1β is an inflammatory sensor of Seneca Valley Virus 3C Protease. PLOS Pathogens (2024).