Elafin

Elastase-specific inhibitor (ESI), skin-derived antileukoproteinase (SKALP), peptidase inhibitor 3 (PI3), trappin-2 (the full-length precursor; elafin is its C-terminal domain), WAP four-disulfide core domain protein 14 (WFDC14)

Skin & cosmetic

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Naturally occurring 57-amino-acid human protein (6 kDa) of the whey-acidic-protein (WAP) family; released from the 95-amino-acid precursor trappin-2 (pre-elafin); produced by skin keratinocytes, airway and gut epithelium
Mechanism: Potently and selectively inhibits the neutrophil enzymes elastase and proteinase 3, limiting tissue destruction; also has antimicrobial, anti-inflammatory (NF-κB-dampening) and immune-modulating actions
Routes studied: Intravenous (human Phase 1 and 2); topical, intratracheal and gene delivery in animals; engineered bacteria delivering elafin to the gut in mice
Half-life: Short in plasma (minutes to ~1 h) as a small protein; stays longer in tissue because trappin-2 can be cross-linked to extracellular matrix by transglutaminase
Storage: Recombinant protein: frozen or refrigerated per manufacturer; a research reagent, not a consumer product
Regulatory status: Investigational; EU orphan designations (pulmonary arterial hypertension; oesophageal cancer surgery); not approved anywhere

Doses are as reported in studies or by the community — never recommendations.

1What it is

Elafin is a small protein the body makes in skin and on mucosal surfaces as a brake on neutrophil enzymes. Neutrophils (first-responder white cells) release elastase and proteinase 3 to kill bacteria, but these enzymes also chew through healthy tissue; elafin and its relative SLPI (secretory leukocyte protease inhibitor) keep that damage local. It was discovered in the late 1980s in the scaly skin of psoriasis (hence "skin-derived antileukoproteinase") and in airway secretions. Its levels rise in inflamed skin, in lungs during infection and in the gut, and fall or become overwhelmed in some inflammatory diseases.

A recombinant human elafin was developed by a German biotechnology company from the 2000s, with Phase 1 and Phase 2 trials and EU orphan drug designations. Elafin is also well known as a biomarker: blood elafin is a validated marker of skin graft-versus-host disease after bone marrow transplant. It is an endogenous human protein, not a synthetic research compound, and it has no consumer or community use.

2How it's thought to work

Protease inhibition. binds neutrophil elastase and proteinase 3 tightly and irreversibly in practice, protecting elastin, collagen and cell junctions (Wiedow 1990).

Anti-inflammatory signalling. reduces NF-κB activation and release of IL-8, TNF-α and other cytokines from epithelial and endothelial cells, independent of protease inhibition in some models.

Antimicrobial. kills or opsonises Gram-negative and Gram-positive bacteria and fungi at micromolar concentrations.

Matrix anchoring. the "cementoin" domain of trappin-2 is cross-linked into extracellular matrix by transglutaminases, creating a local, long-lasting protease shield.

Immune modulation. promotes resolution of inflammation and modulates macrophage phenotype in lung injury models.

An elastase inhibitor made by epithelium. It sits in the active site of neutrophil elastase, so the enzyme cannot cut the elastin that gives lung and skin their recoil — a local brake on the damage inflammation does to structure.Schematic — not to scale

3What the research shows

Graded B (Phase 2, not fully published)

Inflammation after oesophagectomy for oesophageal cancer

A randomised, placebo-controlled Phase 2 trial at the University of Kiel tested IV elafin around surgery to blunt the post-operative inflammatory response. The sponsor announced that recruitment was completed and later reported shorter intensive-care stay in elafin-treated patients †; a full peer-reviewed publication with primary endpoint data has not been identified as of review date. Treat as a positive sponsor announcement, B at most.

Graded B/C

Kidney transplantation and cardiac surgery

A Phase 2 study of elafin to protect kidney grafts from ischaemia-reperfusion injury was planned or started in Germany †. Experimental work in porcine and rodent cardiac surgery models showed reduced myocardial injury.

Phase 1 safety

A single-dose escalation study in healthy volunteers reported good tolerability.

Graded C (EU orphan designation)

Pulmonary arterial hypertension

Elafin-overexpressing mice are protected from hypoxic pulmonary hypertension, and recombinant elafin reversed vascular remodelling in rodent PAH models (Nickel 2015, Am J Respir Crit Care Med). No completed human trial. [7]

Inflammatory bowel disease and coeliac disease

Elafin expression is reduced in inflamed gut of IBD and coeliac patients; delivering elafin via engineered food-grade bacteria protected mice from chemically induced colitis and gluten-related damage (Motta 2012, Sci Transl Med; Galipeau 2014, Am J Gastroenterol). Human data are observational. [5][6]

Graded C/D

Skin: psoriasis, wound healing, dermatitis

Elafin is strongly upregulated in psoriatic plaques and wound edges; topical or gene-delivered elafin reduces inflammation in mouse skin models. No human treatment trials. Despite "skin" in its name, there are no cosmetic or dermatological products containing elafin.

Graded A (as a diagnostic)

Graft-versus-host disease (biomarker)

Plasma elafin is a validated biomarker of skin GVHD and predicts outcomes (Paczesny 2010, Sci Transl Med). This is diagnostic use, not treatment. [4]

Lung injury, ARDS, cystic fibrosis

Elafin deficiency or cleavage is documented in ARDS and CF airways; recombinant or gene-delivered elafin protects in rodent and pig lung-injury models. No human treatment trial.

4Reported side effects and interactions

Literature-reported

Phase 1 reported no significant adverse events; detailed Phase 2 safety not published. As a human protein, antibody formation is the main theoretical risk with repeated dosing. Elafin can be cleaved and inactivated by bacterial and host proteases in heavily infected tissue.

Community-reported

essentially none documented; elafin is not sold or used outside laboratories and trials.

Theoretical. blunting neutrophil proteases could impair host defence during active infection; interplay with alpha-1 antitrypsin pathways.

Interactions. none established.

Markers researchers commonly monitor

Community use is essentially none, so these reflect the trial endpoints and the biology:

Marker	Why it's watched
CRP, IL-6, IL-8, procalcitonin	the systemic inflammatory markers the surgical trials measured.
Neutrophil elastase activity or elastase–inhibitor complexes	a direct pharmacodynamic readout used in research.
Plasma elafin itself	relevant as a GVHD biomarker in transplant patients, not as a drug-monitoring tool.
Anti-drug antibodies	the standard concern with repeated protein dosing.
Organ function (creatinine, troponin, oxygenation)	in the surgical and transplant indications studied.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Recombinant elafin is a research reagent and clinical-trial product supplied frozen or by laboratories, handled under sterile conditions. There is no community formulation, no vial sizes in circulation and no self-administration protocol; the calculator does not apply.

6Commonly studied alongside

SLPI (its sister protease inhibitor), alpha-1 antitrypsin (the systemic elastase inhibitor; approved for AAT deficiency), LL-37 and other antimicrobial peptides (profiles in Tier 3), thymosin beta-4 (profile 2) as a comparator in wound-healing models, KPV (profile in set 2) in colitis models.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Investigational; not FDA-approved; no IND-stage trials identified †
European Union	Investigational; EMA orphan designations for pulmonary arterial hypertension / CTEPH (2007–2008) and for oesophageal carcinoma surgery (2011–2012) †; not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Not listed by WADA; as a non-approved substance would fall under S0

8Open questions

Full publication of the oesophagectomy Phase 2 data.
Whether local delivery (inhaled, topical, gut-targeted bacteria) can overcome the short plasma .
Elafin's role in PAH, where orphan status exists but human trials have not followed.
Whether its biomarker role in GVHD can be turned into a therapeutic one.

9References

1Wiedow O et al. (1990). Elafin: an elastase-specific inhibitor of human skin. Purification, characterization, and complete amino acid sequence. J Biol Chem. PubMed
2Sallenave JM (2010). Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity. Am J Respir Cell Mol Biol. PubMed · DOI
3Shaw L, Wiedow O (2011). Therapeutic potential of human elafin. Biochem Soc Trans. PubMed · DOI
4Paczesny S et al. (2010). Elafin is a biomarker of graft-versus-host disease of the skin. Sci Transl Med. PubMed · DOI
5Motta JP et al. (2012). Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis. Sci Transl Med. PubMed · DOI
6Galipeau HJ et al. (2014). Novel role of the serine protease inhibitor elafin in gluten-related disorders. Am J Gastroenterol. PubMed · DOI
7Nickel NP et al. (2015). Elafin reverses pulmonary hypertension via caveolin-1-dependent bone morphogenetic protein signaling. Am J Respir Crit Care Med. PubMed · DOI
8Verrier T et al. (2012). The WAP protein trappin-2/elafin: a handyman in the regulation of inflammatory and immune responses. Int J Biochem Cell Biol. PubMed · DOI
9Proteo Biotech AG press releases on Phase 1 and Phase 2 elafin trials and EMA orphan designations (sponsor communications; to be replaced by peer-reviewed sources where available). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

31 Oct 2026Profile published — awaiting medical review

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