Human Interleukin 8

Summary

Human interleukin‑8 (IL‑8, also called CXCL8) is a CXC chemokine that attracts and activates neutrophils. Produced by many cell types in response to inflammatory stimuli such as IL‑1, TNF‑α or bacterial products, IL‑8 is used in research to study neutrophil chemotaxis, model inflammatory lung injury, and as a radiolabelled probe for detecting bacterial infection. A fully human anti‑IL‑8 monoclonal antibody (ABX‑IL8) has been investigated in inflammatory disease trials.

Mechanism of Action

IL‑8 binds to the G‑protein‑coupled receptors CXCR1 and CXCR2 on neutrophils and other leukocytes. Receptor activation triggers calcium influx and downstream MAP‑kinase and PI3‑kinase pathways, leading to rapid chemotaxis, degranulation and respiratory‑burst activity. Transcription of the IL‑8 gene is up‑regulated by NF‑κB and C/EBP elements in its promoter after stimulation with IL‑1, TNF‑α or phorbol esters. In vivo, systemic IL‑8 can cause pulmonary neutrophil sequestration and edema resembling acute respiratory distress syndrome.

What the Research Shows

Animal studies showed that intradermal or intravenous human IL‑8 induces concentration‑dependent neutrophil infiltration, peaking four hours after administration, and can cause lung neutrophil sequestration and edema in rabbits. In vitro, recombinant IL‑8 restores defective neutrophil killing, oxidative burst and chemiluminescence in cells from myelodysplastic syndrome patients without markedly stimulating myeloid progenitors. A pilot clinical imaging study injected ^131I‑labeled IL‑8 intravenously into diabetic patients with osteomyelitis or cellulitis; focal uptake was observed in all active infections but not in healed lesions or degenerative disease. A fully human IgG2 antibody (ABX‑IL8) that binds IL‑8 was evaluated in psoriasis and rheumatoid arthritis patients, demonstrating linear pharmacokinetics and no anti‑drug antibodies. Recent work identified recombinant CCSP as a protein that can bind IL‑8 and attenuate its neutrophil‑attracting activity in COPD models.

Reported Benefits

IL‑8 is a potent neutrophil chemoattractant, making it valuable for studying innate immune mechanisms and for developing diagnostic tools; radiolabelled IL‑8 has shown ability to localise active bacterial infections in a small human cohort. In vitro, IL‑8 can correct functional deficits of neutrophils from myelodysplastic syndrome patients, suggesting a supportive role without strong progenitor stimulation. The anti‑IL‑8 antibody ABX‑IL8 exhibits predictable pharmacokinetics and an immunogenicity‑free profile, supporting its further exploration as a therapeutic modulator of IL‑8‑driven inflammation.

Limitations of the Evidence

Evidence for clinical applications remains limited. The infection‑imaging study involved only eleven patients and lacked comparison with standard imaging modalities. The restorative effect on MDS neutrophils was demonstrated only in vitro, with no clinical outcome data. ABX‑IL8 has been studied solely for pharmacokinetics; efficacy in reducing disease activity has not been reported. Animal models indicate that high systemic IL‑8 can provoke lung edema, raising safety concerns for systemic administration. Overall, the therapeutic potential of IL‑8 modulation is still speculative and requires larger, controlled trials.

Safety Considerations

Systemic administration of recombinant IL‑8 in rabbits produced neutrophil sequestration in the lungs and, after repeated dosing, septal and intra‑alveolar edema resembling acute respiratory distress syndrome, indicating a risk of pulmonary injury. Radiolabelled ^131I‑IL‑8 introduces radiation exposure, though the pilot study reported no acute adverse events. In the ABX‑IL8 pharmacokinetic trial, no anti‑drug antibodies or dose‑related toxicities were observed, suggesting a favorable safety profile for the antibody. Nonetheless, modulation of a key inflammatory chemokine could theoretically exacerbate infections or impair host defence, and safety in broader patient populations remains uncharacterized.

How It Is Administered

Recombinant IL‑8 has been administered intravenously in human studies, including as a ^131I‑labelled tracer for infection imaging. The anti‑IL‑8 monoclonal antibody ABX‑IL8 was given by short intravenous infusion in patients with psoriasis or rheumatoid arthritis. Formulations described in the literature are protein solutions intended for parenteral use; no oral or inhaled preparations have been reported.

Routes of Administration

No administration routes recorded yet.

Goals & Uses

• Biomarker for infection/inflammationDiagnosticHigh
• Research biomarker for inflammationBiomarker / DiagnosticsHigh
• Therapeutic target in oncologyAnti CancerModerate
• Modulate neutrophil chemotaxisAnti‑inflammatoryModerate
• Wound healing / angiogenesis researchTissue RepairLow
• Therapeutic target for inflammatory diseasesAnti InflammatoryModerate

Contraindications

• Not applicable as therapeutic agentGeneralHigh

Adverse Effects

• Pro-inflammatory cytokine storm contributionImmunologicalUnknown
• Neutrophil-mediated tissue damageImmunologicalUnknown
• Promotion of tumor angiogenesisOncologicalUnknown

Drug Interactions

• Anti-IL-8 monoclonal antibodies (e.g., BMS-986253)Low
• CXCR1/CXCR2 antagonists (e.g., reparixin, navarixin)Low

Population Constraints

• Not for therapeutic use in any populationGeneral PopulationAbsolute

Regulatory Status

• European UnionUnapprovedNot approved by EMA as a therapeutic. Research and investigational use only.
• United StatesUnapprovedNot approved by FDA as a therapeutic. Used as a research reagent and biomarker. Anti-IL-8 therapies are in investigational trials.
• United KingdomUnapprovedNot approved by MHRA as a therapeutic. Research and biomarker use only.

IL-8 (CXCL8) is not approved as a therapeutic agent in any jurisdiction. It is used as a biomarker and research tool. Anti-IL-8 antibodies (e.g., BMS-986253/HuMax-IL8) and CXCR1/CXCR2 antagonists targeting this pathway are in clinical trials.

Evidence & Sources

• Imaging of human infection with (131)I-labeled recombinant human interleukin-8
  Journal ArticleModerateGross MD, et al.2001-01-01T00:00:00.000000Z
• In vitro and in vivo activity and pathophysiology of human interleukin-8 and related peptides
  Journal ArticleModerateZwahlen R, Walz A, Rot A1993-01-01T00:00:00.000000Z
• Population pharmacokinetic evaluation of a fully human IgG monoclonal antibody in patients with inflammatory diseases
  Journal ArticleModerateTabrizi M, et al.2010-01-01T00:00:00.000000Z
• Regulation of human interleukin 8 gene expression and binding of several other members of the intercrine family to receptors for interleukin-8
  Journal ArticleModerateMukaida N, et al.1991-01-01T00:00:00.000000Z
• Recombinant human interleukin-8 restores function in neutrophils from patients with myelodysplastic syndromes without stimulating myeloid progenitor cells
  Journal ArticleModerateZwierzina H, et al.1993-01-01T00:00:00.000000Z
• CCSP counterbalances airway epithelial-driven neutrophilic chemotaxis
  Journal ArticleModerateKnabe L, et al.2019-01-01T00:00:00.000000Z

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