LL-37Cathelicidin · the only human host-defense peptide — a wound-research lane, not an immune protocol
LL-37 is a natural immune peptide the human body makes itself to defend skin and mucosal surfaces against microbes and to help repair wounds. It is the only human cathelicidin antimicrobial peptide. Its most credible human research is in topical wound care — venous leg ulcers and diabetic foot ulcers. It is not a general "immune booster," and Intrasigna blocks all injectable, systemic, oral, intranasal, and personalized-dosing output for it.
LL-37 is a pleiotropic host-defense peptide with antimicrobial, antibiofilm, chemotactic, endotoxin-neutralizing, angiogenic, epithelial-repair, and immunomodulatory effects whose biology is highly context-dependent. Topical LL-37 was safe with dose-response healing in a 2014 venous-leg-ulcer RCT, though a larger phase-IIb trial (HEAL, n=148) found no significant full-cohort difference, with a possible large-ulcer subgroup signal. In inflammatory skin disease it can act as an autoantigen/immune amplifier (psoriasis, lupus) — so the page is research-only and hard-gated.
LL-37 (sequence LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) is a 37-residue cationic (+6), amphipathic, cysteine-free α-helix released from the hCAP18 precursor (gene CAMP, chr 3p21.3) by proteinase 3. It disrupts microbial membranes via cationic/amphipathic interactions, engages FPR2/FPRL1 chemotaxis, neutralizes LPS, drives keratinocyte migration via EGFR transactivation, and forms immunostimulatory complexes with self-DNA/RNA that activate pDCs via TLR9 → type-I interferon — beneficial in defense and repair, but pro-inflammatory and tumor-context-dependent elsewhere.
37 aaCationic +6 · amphipathic α-helix
hCAP18 / CAMPOnly human cathelicidin
topicalStrongest human lane (wounds)
BLOCKEDHuman dosing output
Status
Research-only · topical trial-arm display only · injectable/systemic blocked
RESEARCH-ONLY · human dosing output is BLOCKED
LL-37 is an endogenous human host-defense peptide whose strongest human research is topical wound care. Intrasigna blocks public injectable, systemic, intranasal, oral, and personalized-dosing output because immune activation, autoimmune signaling, cancer-context uncertainty, cytotoxicity, and formulation stability remain unresolved. Only source-backed topical clinical-trial arms are displayed, as research context — never a treatment recommendation.
01 · At a glance
A rich mechanism, hard-gated.
LL-37 is one of the most biologically interesting peptides in this atlas and one of the most tightly gated. Its wound-repair and antimicrobial biology is genuinely compelling and human-tested topically, but the same immune potency that helps in defense can amplify autoimmune and inflammatory disease — and its cancer biology cuts both ways. Intrasigna therefore publishes it as an advanced-research / immune & wound-biology page with a topical trial-arm reference engine, not a dosing protocol.
🧬
Identity
Only human cathelicidin
A 37-aa peptide cleaved from hCAP18 (gene CAMP) — the sole human cathelicidin. Grade A/B.
🦠
Antimicrobial
Membrane disruption
Cationic/amphipathic disruption of microbial membranes; broad-spectrum + antibiofilm. Grade B.
🩹
Wound repair
Re-epithelialization
Promotes keratinocyte migration; deficient in chronic ulcer epithelium. Grade B.
🧪
Human lane
Topical wounds
VLU and DFU topical trials — the only source-backed human dosing context. Grade B/C.
⛔
Human dosing
Blocked
Injectable, systemic, oral, intranasal, and protocol output are blocked. Admin rule.
Pro-tumor in some tissues, suppressive in others — never an anti-cancer claim. Risk.
🛠️
Development limit
Cytotoxic / unstable
Eukaryotic cytotoxicity and proteolytic instability constrain therapeutic use. Grade C.
02 · Mechanism of action
One peptide, a whole defense program.
LL-37 is a paradigm "pleiotropic" host-defense peptide: a single small α-helix that kills microbes, breaks biofilms, recruits and tunes immune cells, neutralizes endotoxin, drives wound repair and new blood vessels — and, in the wrong context, amplifies sterile inflammation and autoimmunity. The same cationic, amphipathic chemistry that disrupts microbial membranes is what makes its biology so context-dependent.
Grade B
🦠
1 · Direct antimicrobial membrane disruption
Its positive charge pulls it onto microbial membranes, which it then permeabilizes.
Clinical significance: The cationic, amphipathic helix binds anionic microbial membranes and disrupts them, killing a broad range of Gram-positive and Gram-negative bacteria, including some antibiotic-resistant strains. It also contributes to respiratory, oral-cavity, and antimycobacterial defense at epithelial surfaces.
Molecular detail: Killing is described by carpet/toroidal-pore models — the helix's hydrophobic face inserts into the lipid bilayer while cationic residues anchor anionic head-groups, causing permeabilization. LL-37 is found in neutrophils, epithelia, sweat, saliva, wound fluid, and seminal plasma.
Grade B/C
🧫
2 · Antibiofilm activity
It can prevent and disrupt the protective biofilms bacteria build on wounds and surfaces.
Clinical significance: LL-37 shows strong preclinical antibiofilm activity — relevant to chronic wounds — though clinical antibacterial effect was inconsistent in the diabetic-foot-ulcer trial.
Molecular detail: LL-37 interferes with biofilm attachment, quorum-sensing signaling, and extracellular matrix integrity at sub-bactericidal concentrations; formulation and stability limit translation to durable wound-surface effect.
Grade B
🩹
3 · Keratinocyte migration & re-epithelialization
It signals skin cells to migrate and close wounds — and is missing where ulcers won't heal.
Clinical significance: LL-37 promotes keratinocyte migration and re-epithelialization of human skin wounds and is deficient in chronic ulcer epithelium — the core rationale for the wound-research lane.
Molecular detail: Migration is linked to EGFR transactivation and downstream ERK signaling; maximal keratinocyte migration was reported around 1 µg/mL in a Boyden-chamber assay — strictly in-vitro mechanistic context, not a human dose.
Grade B
🩸
4 · Angiogenesis & endothelial activation
It helps grow the new blood vessels that feed healing tissue.
Clinical significance: LL-37 activates endothelial cells and promotes neovascularization in experimental models, supporting granulation-tissue formation in wounds.
Molecular detail: Pro-angiogenic effects involve FPR2-dependent endothelial activation and VEGF/PI3K–AKT signaling; topical synthetic/recombinant LL-37 increased vascularization and re-epithelialization in preclinical wound models.
Grade C
🧭
5 · Chemotaxis & LPS neutralization
It calls in immune cells and can mop up bacterial endotoxin.
Clinical significance: LL-37 recruits immune cells via FPR2/FPRL1 chemotaxis and binds and neutralizes LPS/endotoxin — bridging innate and adaptive immunity. This is mechanistic, not a sepsis-therapy claim.
Molecular detail: As an "alarmin," LL-37 chemoattracts neutrophils, monocytes, and T cells; it is a component of neutrophil extracellular traps (NETs) and modulates TLR responses to microbial ligands.
Grade C · Risk
🔥
6 · Nucleic-acid immune amplification (risk)
Bound to the body's own DNA/RNA, it can switch on sterile inflammation and autoimmunity.
Clinical significance: LL-37 complexes with self-DNA/RNA and lets plasmacytoid dendritic cells recognize them via TLR9/TLR7, driving type-I interferon — a central mechanism in psoriasis and a major safety flag.
Molecular detail: In lupus, NET-derived DNA–LL-37 complexes and anti-LL-37 antibodies amplify pDC activation and type-I IFN; LL-37 also presents RNA to scavenger receptors (e.g., SR-B1) on keratinocytes, forming ordered supramolecular complexes that potentiate sensing.
L3 · Dual-edged cascade
From host-defense peptide to context-dependent outcome
🧬 LL-37
hCAP18 · proteinase 3
→
🦠 Defense
microbial · LPS · chemotaxis
→
🩹 Repair
re-epithelialization · vessels
⇄
🔥 Inflammation
pDC · TLR9 · IFN
→
⚖️ Context outcome
benefit or harm
L2 · Mechanism map
Mechanism clusters & protocol relevance
Cluster
Action
Relevance / grade
Antimicrobial
Membrane disruption, antibiofilm
Wound-infection lane · B
Epithelial repair
Keratinocyte migration (EGFR/ERK)
Chronic-wound lane · B
Angiogenesis
Endothelial activation, VEGF/PI3K–AKT
Granulation/perfusion · B
Immune recruitment
FPR2 chemotaxis, NET component
Inflammation monitoring · C
Endotoxin binding
LPS neutralization
Mechanistic only · C
Nucleic-acid sensing
pDC/TLR9 → type-I IFN
Autoimmune risk flag · C
L3 · receptor & signaling partners
Reported interaction systems
Partner
Effect
Context
FPR2 / FPRL1
Chemotaxis, endothelial activation
Immune recruitment, angiogenesis
EGFR / ErbB
Transactivation → migration
Keratinocyte re-epithelialization
TLR9 / TLR7 (via pDC)
Self-nucleic-acid sensing
Psoriasis / lupus risk
Scavenger receptor (SR-B1)
RNA presentation
Keratinocyte IFN response
P2X7 / inflammasome
Inflammatory signaling
Context-dependent
LPS (direct binding)
Endotoxin neutralization
Anti-endotoxic (mechanistic)
03 · Protocol engine & research lanes
A route-gated research engine — not a dosing protocol.
LL-37 is not a "blocked" page — it is a structured topical wound-research engine with hard gates. The panels below are the engine's lanes: the venous-leg-ulcer and diabetic-foot-ulcer human trial arms (displayed as research context only), the antimicrobial/biofilm mechanistic lane, the eligibility & safety gate logic, and the explicitly blocked routes. The engine displays trial concentrations, schedules, durations, and endpoints with citations — it never generates a personalized dose, an injectable dose, a cycle, or reconstitution math.
Engine mode · trial-only topical research
The calculator is a topical trial-arm reference, gated by route, wound type, infection severity, vascular status, autoimmune and cancer history, and provider/IRB review. Topical VLU/DFU arms display as research context; injectable, systemic, oral, intranasal, and "immune protocol" routes all return BLOCKED.
Evidence honesty
The engine deliberately shows mixed efficacy. A 2014 RCT found topical LL-37 safe with dose-response healing in hard-to-heal VLUs, but the larger HEAL phase-IIb trial (n=148) found no significant full-cohort difference, with only a possible large-ulcer subgroup signal. The DFU RCT improved granulation but did not reduce cytokines or bacterial colonization.
Display as clinical-trial context only. Block if uncontrolled infection, poor perfusion, autoimmune flare, or malignancy concern.
VLU · trial arms
Source-backed concentrations
Arm
Schedule
Basis
0.5 mg/mL
2×/week · 4 wk
RCT arm
1.6 mg/mL
2×/week · 4 wk
RCT arm
Full cohort (HEAL IIb)
—
NS; subgroup signal
Lane B — Diabetic foot ulcer research
Topical cream · 0.5 mg/g · twice weekly · 4 weeks
Grade B/C
Research status
Human topical trial lane (RCT) — trial-arm display only.
Concentration
LL-37 cream 0.5 mg/g, twice weekly for 4 weeks.
Population
Diabetic foot ulcer with mild infection (trial context).
Primary signal
Improved granulation index across days 7, 14, 21, 28 and healing rate.
Negative findings
No significant reduction in IL-1α, TNF-α, or aerobic bacterial colonization.
Tolerability
No side effect directly attributed to LL-37 cream; one mild irritant dermatitis tied to wound exudate.
Requires diabetes control, vascular status (ABI), infection-severity assessment, and wound-care supervision. Block in severe/deep infection or osteomyelitis.
DFU · trial arm & endpoints
Source-backed cream protocol
Field
Value
Source
Concentration
0.5 mg/g cream
RCT
Schedule
Twice weekly · 4 wk
RCT
Primary endpoint
Granulation index
RCT
Inclusion (perfusion)
ABI 0.9–1.3
Trial criterion
Lane C — Antimicrobial / biofilm research
Mechanistic / preclinical
Grade C
Research status
Preclinical/mechanistic — mostly topical/local models; no broad human infection-treatment protocol.
Spectrum
Antimicrobial activity against Gram-positive and Gram-negative pathogens, including resistant strains.
Biofilm
Antibiofilm activity at sub-bactericidal concentrations in preclinical models.
MRSA
Mouse wound-infection model evidence only — not a human protocol; no human dose conversion.
Antimicrobial/biofilm activity does NOT create a human infection-treatment protocol. Output is mechanism summary only unless tied to a wound-trial context.
Preclinical · status
Model-to-human gating
Model
Status
Human conversion
In-vitro antimicrobial
Mechanistic
None
Biofilm assays
Preclinical
None
MRSA mouse wound
Animal
Blocked
Eligibility & safety gate logic
Engine decision tree
Admin
Route gate
Injectable/systemic/oral/intranasal → BLOCK (no source-backed human systemic dosing basis).
Indication gate
General immunity / anti-aging / wellness → BLOCK (no clinical protocol basis).
Wound-type gate
Topical + VLU or DFU → allow trial-arm display only.
Autoimmune / cancer gate
Psoriasis, lupus/SLE, active autoimmune flare, or active cancer → block or provider-review-only.
Infection-severity gate
Systemic/deep infection, osteomyelitis, severe cellulitis → block; requires standard care, not a substitute for antibiotics/debridement.
Final output shows trial concentration, frequency, duration, endpoints, exclusions, and citations — never personalized/injectable dosing, cycles, or reconstitution.
Engine · decision tree
Gate sequence
Step
Gate
Action
1
Route
Block non-topical
2
Indication
Block wellness/immune
3
Wound type
Allow VLU/DFU display
4
Autoimmune/cancer
Block / provider review
5
Infection severity
Block severe/deep
6
Vascular
Block poor perfusion
7
Output
Trial-arm display only
Blocked routes & outputs
No human dosing basis
Grade E · blocked
Injectable / systemic
Blocked — no approved or source-backed human systemic dosing basis.
Intranasal / oral
Blocked — peptide degradation and no dosing basis; mechanistic claims only.
"Immune protocol"
Blocked — no protocol output; LL-37 is not a general immune booster.
Cancer / autoimmune protocol
Blocked — context-dependent biology; not a therapy claim.
Reconstitution / mixing
Blocked — no preparation guidance without a pharmacy/clinical formulation source.
Why: eukaryotic cytotoxicity and proteolytic instability/formulation challenges limit therapeutic development; systemic safety is unresolved.
Route · status table
Output rules by route
Route
Status
Output
Topical wound (VLU/DFU)
Trial-only
Study arm + citation
Injectable / systemic
Blocked
No human dose
Intranasal / oral
Blocked
No human dose
"Immune protocol"
Blocked
No protocol
Animal model
Research-only
No human conversion
L2 · Topical trial-arm reference · human output blocked
Trial-Arm Reference Engine
LL-37 is an investigational host-defense peptide with immune-activating and tissue-context-dependent effects. Public dosing, injectable protocols, and personalized treatment output are blocked. Only source-backed topical clinical-trial arms may be shown for educational review. Selecting any non-topical route returns BLOCKED. This is research context, not a treatment recommendation.
Trial concentration
—
Frequency
—
Duration
—
Model
—
Basis
—
04 · Combinations & interaction logic
Bidirectional immune effects — no public stacks.
LL-37 has bidirectional immune effects, so Intrasigna publishes no public stack recommendations for it. It should not be auto-combined with immune peptides, wound peptides, antimicrobials, or metabolic peptides without a safety note and provider review — especially in autoimmune, inflammatory-skin, cancer, or infected-wound contexts.
+ BPC-157 / TB-500
Blocked / research-only
LL-37BPC-157TB-500
A popular "wound-repair stack" idea — but there is no source-backed combination safety data. Blocked / research-only; do not present as validated synergy. Grade E.
Element
Status
Reason
BPC-157 / TB-500
Block
No combo safety source
+ Antibiotics
Provider-only
LL-37Antibiotics
LL-37 does not replace antibiotics or debridement. Any adjunct research context is provider-only; standard infection care takes precedence. Grade C.
Element
Role
Gate
Antibiotics
Standard care
Provider-only
+ GHK-Cu (topical)
Research-only
LL-37GHK-Cu
Both appear in wound/cosmetic discussion, but combined wound-healing synergy is not source-backed. Avoid overstating; research-only. Grade C.
Element
Status
Note
GHK-Cu
Research-only
No synergy claim
+ Steroids / Immunosuppressants
Provider-only
LL-37Immunosuppressants
LL-37's immune-activating effects can conflict with immunosuppressive therapy; clinical context is required. Provider-only. Grade C.
Element
Concern
Gate
Steroids / IS
Conflicting immune effects
Provider-only
+ Vitamin D
Research / observational
LL-37Vitamin D
Vitamin D (via VDR) directly induces CAMP/LL-37 expression, and serum LL-37 has correlated with VLU healing — but adequate vitamin D status is not a dosing substitute or protocol. Grade C.
Element
Relationship
Gate
Vitamin D
Induces CAMP expression
Not a dose substitute
+ Anti-inflammatory peptides
Blocked
LL-37Anti-inflammatory peptides
Risk of contradictory immune effects; combining is blocked without clinical review given LL-37's pro-inflammatory potential in some contexts. Grade E.
Element
Status
Reason
Anti-inflammatory peptides
Block
Contradictory effects
+ Other GLP-1 / metabolic peptides
Blocked / no basis
LL-37Metabolic peptides
No source-backed rationale to combine LL-37 with metabolic peptides; blocked as an unsupported stack. Grade E.
Element
Status
Reason
Metabolic peptides
Block
No basis
General "immune-boost" stacking
Blocked
LL-37Immune protocol
LL-37 is not a casual immune booster; general immune-stacking protocols are blocked. Its immune effects are bidirectional and context-dependent. Grade E.
Use
Status
Reason
Immune-boost stack
Block
No protocol basis
Stack warning — LL-37 has bidirectional immune effects. Do not combine it with immune-active peptides or antimicrobial protocols without clinical review, especially in autoimmune, inflammatory-skin, cancer, or infected-wound contexts.
05 · Safety & contraindications
One of the atlas's strongest safety gates.
LL-37 needs aggressive safety gating because the very potency that makes it useful in defense and repair can push immune activation in harmful directions. The dominant concerns are autoimmune/inflammatory amplification (psoriasis, lupus), context-dependent cancer biology, eukaryotic cytotoxicity, and the fact that topical wound research never replaces standard infection or vascular care.
⛔ Research-only — LL-37 can act as an autoantigen/immune amplifier in psoriasis and lupus-type pathways and has tissue-specific, contradictory cancer biology. Human dosing output is blocked; only topical clinical-trial arms are shown as research context. Provider review is required for any clinical-research use.
Core safety risks
Autoimmune activationSelf-DNA/RNA complexes drive pDC/TLR9 type-I IFN — high concern.
Psoriasis worseningActs as autoantigen/immune amplifier; LL-37-specific T cells track disease activity.
ThromboinflammationCathelicidin biology reviewed in thrombosis/thromboinflammatory disorders.
Local irritation / dermatitisPossible wound-environment irritation; monitor skin response.
Proteolytic instabilityDegradation limits wound persistence and drug development.
Inconsistent antibacterial effectDFU trial showed no significant bacterial-colonization reduction.
Cardiometabolic inflammation contextExcess LL-37 in inflammatory skin disease has been linked to altered lipid biology.
Not an antibiotic replacementSevere/deep infection and osteomyelitis require standard care.
Evidence-grade summary
Evidence · by bucket
How strong is each claim class
Evidence bucket
Grade
Confidence
Endogenous biology / identity
A/B
High (~90)
Antimicrobial mechanism
B
~80
Antibiofilm mechanism
B/C
~70
Human wound biology / re-epithelialization
B
~75
Topical VLU clinical research
B
~70 (mixed by trial)
Topical DFU clinical research
B/C
~65
Injectable / systemic human use
E · blocked
~5
General immune boosting
E · blocked
~5
Autoimmune benefit claims
D · risk
~10
Cancer therapy claims
D/E · risk
~10
Dose-basis records (engine source cards)
Dose-basis · trial-only
What the engine may display vs block
Basis
Arm
Human output
Clinical trial (VLU)
0.5 & 1.6 mg/mL, 2×/wk, 4 wk
false (display only)
Clinical trial (DFU)
Cream 0.5 mg/g, 2×/wk, 4 wk
false (display only)
Injectable / systemic
No basis
false · blocked
Animal model (MRSA)
Mouse wound
false · no conversion
Autoimmune / cancer protocol
Not supported
false · blocked
Eligibility & biomarker engine
Biomarkers · wound-research eligibility
Baseline context the engine requires
Category / marker
Purpose
Gate
Wound type (VLU/DFU/etc.)
Determines trial-lane relevance
Selection
Wound size / duration / depth
Chronicity, endpoint baseline
Selection
Infection severity + wound culture
Blocks severe/deep infection
Safety gate
ABI / perfusion
Blocks poor perfusion (DFU inclusion ABI 0.9–1.3)
Safety gate
HbA1c / fasting glucose
Required for DFU lane
Context
CRP / ESR
Systemic inflammatory burden
Monitor
CBC with differential
Infection / immune status
Baseline
ANA / anti-dsDNA
Autoimmune/lupus screen if indicated
Safety gate
Autoimmune / psoriasis history
Exclusion logic
Safety gate
Cancer history
Exclusion / oncology review
Safety gate
IL-1α / TNF-α / IL-6 (research)
Wound-fluid inflammatory markers
Research endpoint
Monitoring endpoints
Wound-healing endpoints
Wound-area reduction (objective measurement), granulation index (key DFU outcome), re-epithelialization percentage, drainage/exudate, and pain score for tolerability — tracked across the study window.
Safety / infection
Signs of infection (redness, warmth, drainage, odor, fever), CRP/ESR if systemic concern, and local dermatologic reaction (itching, rash, dermatitis). Escalate to standard care if infection worsens.
Immune-safety surveillance
Watch for autoimmune-flare signals (new rash, worsening plaques, joint pain, photosensitivity, oral ulcers), especially given the psoriasis/lupus risk lane. Provider/IRB review for any clinical-research use.
Contraindications & hard exclusion flags
Condition
Concern
Severity · grade
Injectable / systemic / oral / intranasal use
No source-backed human dosing basis
Blocked
General immune / wellness protocol
No clinical protocol basis
Blocked
Active psoriasis
Amplifies psoriatic immune pathways
Block / review
Lupus / SLE / autoimmune disease
Nucleic-acid immune activation
Block / review
Active autoimmune flare
Immune-activation risk
Block
Active malignancy / cancer history
Tissue-specific, contradictory biology
Block / oncology review
Systemic infection / sepsis
Not an antimicrobial replacement
Block
Deep infected ulcer / osteomyelitis
Requires antibiotics/debridement/imaging
Block protocol
Critical limb ischemia / poor perfusion
Perfusion must be addressed first
Block protocol
Uncontrolled inflammatory skin disease
Immune activation / irritation
Caution / review
Severe allergy / mast-cell disorder
Histamine/mediator concern
High-risk warning
Pregnancy / breastfeeding
No adequate safety basis
Block
Pediatric use
No broad dosing/safety basis
Block
Uncontrolled diabetes (DFU lane)
Healing / infection risk
Optimize first
Mixing / reconstitution request
No formulation source
Blocked
Animal-model → human conversion
Not permitted
Blocked
Non-research / non-provider setting
Provider/IRB review required
Review required
"Loading" / cycle protocol request
No such research concept
Blocked
Combination with immune-active peptides
Contradictory immune effects
Block / review
Thromboinflammatory disorder history
Cathelicidin thrombosis biology
Caution
GRADE summary — LL-37's endogenous biology and antimicrobial/wound mechanisms are well supported (identity A/B; antimicrobial and wound-repair mechanisms B), and topical human wound research is real but mixed (VLU/DFU B–C, with the HEAL phase-IIb trial tempering the earlier positive RCT). Systemic, injectable, immune-boost, autoimmune, and cancer claims are unsupported (D/E) and blocked. The decisive levers are route gating (topical-only), wound-type and vascular/infection eligibility, autoimmune and cancer exclusion, and provider/IRB review — with human dosing output blocked and only source-backed topical trial arms displayed as research context.
06 · Trials & evidence base
Real human data — topical, and mixed.
LL-37's human evidence lives almost entirely in topical chronic-wound trials. An early randomized VLU study was positive on safety and dose-response; a larger phase-IIb VLU trial was not significant in the full cohort; a DFU RCT improved granulation but not cytokines or bacterial colonization. Presenting all three honestly — including the negatives — is what makes the page credible rather than promotional.
No significant full-cohort difference; possible large-ulcer subgroup signal. Mahlapuu 2021.
DFU · RCT
granulation ↑
Cream 0.5 mg/g improved granulation; no cytokine/bacterial reduction. DFU RCT.
Mechanistic
re-epithelialization
Human wound biology + EGFR-driven keratinocyte migration. Wound studies.
BHuman · VLU RCT
Topical LL-37 in hard-to-heal venous leg ulcers (2014)
A randomized, placebo-controlled trial found topical LL-37 safe and showed dose–response efficacy in hard-to-heal venous leg ulcers, testing concentrations including 0.5 and 1.6 mg/mL twice weekly for 4 weeks alongside compression — the strongest early human dosing-basis source.
A double-blind, randomized, placebo-controlled phase-IIb trial in 148 patients with hard-to-heal VLUs (LL-37 + compression) found no significant difference in the full cohort, with a possible benefit signal in a large-ulcer subgroup and no safety concerns — the result that keeps the page from overstating efficacy.
A randomized, double-blind controlled trial of LL-37 cream (0.5 mg/g, twice weekly, 4 weeks) improved the granulation index across days 7–28, but did not significantly reduce IL-1α, TNF-α, or aerobic bacterial colonization; tolerability was good.
LL-37 is the sole human cathelicidin, a 37-residue cationic amphipathic α-helix released from the hCAP18 precursor; the CAMP gene sits on chromosome 3p21.3 and the active peptide is cleaved by proteinase 3 from residues 134–170.
LL-37 promotes keratinocyte migration via EGFR transactivation and re-epithelialization of human skin wounds, and is reportedly deficient in chronic ulcer epithelium — the mechanistic basis for the wound lane.
LL-37 complexes with self-DNA/RNA and enables plasmacytoid dendritic cells to recognize them via TLR9, driving type-I interferon — a central mechanism in psoriasis, with LL-37-specific T cells correlating with disease activity. This is the page's primary risk lane.
Active vitamin D directly induces the CAMP gene encoding LL-37 via a vitamin-D-response element, and serum LL-37 (not 25-OH-vitamin-D) correlated with venous-leg-ulcer healing in a small study — a regulatory relationship, not a dosing substitute.
Eukaryotic cytotoxicity and proteolytic instability, formulation challenges, and production cost limit LL-37's therapeutic development, which is why truncated/engineered analogs (e.g., KR-12, FK-13, GF-17) and local/topical delivery are studied instead of broad systemic use.
LL-37's cationic, amphipathic helix permeabilizes anionic microbial membranes across Gram-positive and Gram-negative pathogens, and shows preclinical antibiofilm activity at sub-bactericidal concentrations — strong rationale that nonetheless did not translate into significant bacterial-colonization reduction in the DFU trial.
LL-37 activates endothelial cells and promotes neovascularization in experimental models (FPR2-dependent, VEGF/PI3K–AKT), supporting granulation-tissue formation — one of the mechanistic legs under the chronic-wound research lane.
As an alarmin, LL-37 chemoattracts neutrophils, monocytes, and T cells via FPR2/FPRL1 and is a component of neutrophil extracellular traps, while binding and neutralizing LPS — mechanistic immune bridging, not a sepsis-therapy claim.
LL-37 shows pro-tumor effects in some cancers and suppressive effects in others, depending on tissue and pathway — contradictory enough that Intrasigna blocks any anti-cancer (or pro-tumor-risk) representation and treats active malignancy as an exclusion.
hCAP18/LL-37 is expressed in neutrophils and squamous epithelia (airway, mouth, esophagus, intestine) and secreted in sweat, saliva, wound fluid, and seminal plasma, with roles in respiratory, oral, and antimycobacterial surface defense — its broad endogenous footprint.
Sequence determinants in LL-37 let it present RNA to scavenger receptors such as SR-B1 on keratinocytes, forming ordered supramolecular complexes that potentiate type-I-interferon responses — extending the self-nucleic-acid immune-amplification mechanism beyond pDCs.
Intrasigna publishes LL-37 with human dosing blocked and only source-backed topical trial arms displayed, behind route, wound-type, infection-severity, vascular, autoimmune, and cancer gates — including vascular assessment (DFU ABI 0.9–1.3) and exclusion of severe/deep infection and osteomyelitis.
LL-37 is often grouped with wound-repair peptides like BPC-157, TB-500, and GHK-Cu, and with antimicrobial peptides like the defensins. The distinction that matters: LL-37 is an immune-active host-defense peptide with genuine human topical wound data but a hard autoimmune/cancer risk profile — so it is gated far more tightly than the popular "wound-repair stack" peptides, and combining them is not source-backed.
L1 · Consumer — LL-37 is a natural immune peptide your body makes to defend skin and surfaces against microbes and to help wounds heal. The most credible human research is topical wound care — leg and diabetic foot ulcers — and even there results are mixed. It is not a general "immune booster," and there is no safe public dose: injectable, systemic, oral, and nasal uses are blocked. It can also worsen immune/inflammatory conditions like psoriasis, so it needs medical oversight.
L2 · Clinical — LL-37 is the only human cathelicidin, a pleiotropic host-defense peptide with antimicrobial, antibiofilm, chemotactic, LPS-neutralizing, angiogenic, epithelial-repair, and immunomodulatory effects. Human evidence is topical-wound only and mixed (positive 2014 VLU RCT; non-significant HEAL phase-IIb full cohort; DFU RCT improved granulation but not cytokines/bacteria). It is hard-gated: route, wound-type, infection severity, perfusion, autoimmune, and cancer gates apply, with provider/IRB review required and human dosing output blocked.
L3 · Research — LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES; 37-aa, +6, amphipathic α-helix from hCAP18/CAMP via proteinase 3) disrupts microbial membranes, neutralizes LPS, drives FPR2 chemotaxis and EGFR-mediated keratinocyte migration, and promotes angiogenesis — while forming self-DNA/RNA complexes that activate pDC TLR9/TLR7 → type-I IFN, the basis of its psoriasis/lupus risk and context-dependent cancer biology. Therapeutic development is constrained by eukaryotic cytotoxicity and proteolytic instability, motivating topical delivery and engineered fragments (KR-12, FK-13, GF-17). Vitamin D/VDR directly induces CAMP expression.
08 · References & evidence
Source register.
Evidence grades reflect the strength of support for the specific claim cited, not the prestige of the journal. LL-37's identity and core mechanisms are well supported; the topical VLU/DFU trials are the firmest human dosing-context sources (and are presented with their negatives); immune-risk, cancer-context, and development-limitation sources anchor the hard safety gating.