Interleukin-1

Origin and synthesis

Cytokine genes are inducible. The main producers of IL-1 are activated macrophages and monocytes at the site of inflammation. Initially, synthesis is triggered by a small number of tissue macrophages, but as leukocytes migrate from the blood, the number of producer cells increases rapidly. Non-immune cells (endothelium, fibroblasts, glia) can also secrete IL-1 when stimulated by microbial products.

Production kinetics is quite rapid:

• mRNA expression begins within 15–30 minutes.
• The protein appears in the cytoplasm within 30–60 minutes.
• Maximum extracellular concentration is reached in 3–4 hours.
• Synthesis is short-lived — usually lasting slightly over a day for an individual cell.

Members of the IL-1 family

The family numbers over 11 molecules, but five are considered active: IL-1α, IL-1β, IL-1RA (receptor antagonist), IL-18, and IL-33.

Traditionally, IL-1 refers to two molecules: IL-1α and IL-1β. They share 26% amino acid sequence homology, bind to the same receptor, and exert identical effects. They are initially synthesized as inactive precursor molecules with a mass of 30 kDa lacking a signal peptide, and upon cleavage of a portion of the chain, they transform into active forms (18 kDa).

Role of the inflammasome

Processing of IL-1β occurs within a specialized protein complex — the inflammasome.

Events unfold in stages:

1. Intracellular NLR receptors (NOD1, NOD2, etc.) recognize pathogen-associated molecular patterns.
2. An inflammasome is formed, comprising receptors and inactive caspase 1.
3. The formation of the transcription factor NF-κB is triggered.
4. Activated caspase 1 cleaves the IL-1β precursor.
5. The mature cytokine (18 kDa) is secreted extracellularly.

Signal transduction and receptors

The receptor apparatus is represented by two types of molecules:

• IL-1RI — the main receptor, expressed in small quantities but having high affinity for the cytokine. The intracellular part features a TIR domain.
• IL-1RII — a decoy receptor lacking a signaling domain (binds IL-1 but does not activate the cell).

Upon binding to IL-1RI, the signal is transduced via MyD88, IRAK, and TRAF6 molecules, leading to the activation of transcription factors NF-κB and AP-1. As a result, pro-inflammatory genes are activated. Importantly, the synthesized inflammatory products cause the cell to release even more IL-1, creating a positive feedback loop.

Effects in the body

The action of IL-1 aims to enhance inflammation without the need for the pathogen to spread throughout the body.

Local effects:

• Stimulation of adhesion molecule expression (facilitates leukocyte emigration from vessels).
• Activation of phagocytosis and the respiratory burst.
• Alteration of vascular tone.

Systemic effects:

• Liver: stimulation of acute-phase protein production.
• Hypothalamus: elevation of body temperature (fever).
• CNS: somnolence, fatigue, loss of appetite.
• Bone marrow: stimulation of hematopoiesis and neutrophil release into the blood (left shift).

Excess IL-1 can destroy cartilage and bone (e.g., in rheumatoid arthritis) or lead to severe conditions resembling septic shock.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Characteristics of the IL-1RII decoy receptor
• Properties and functions of cytokine IL-18
• The role of interleukin-33 (IL-33) in allergic processes
• Interaction of IL-18 and IL-12 in interferon-gamma production
• Amplification of the inflammatory signal

Other topics in the "Innate Immunity" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.