LL-37

Overview

LL-37 is the only known cathelicidin in humans, a class of antimicrobial peptides that form part of the innate immune system. It is the active C-terminal fragment of the precursor protein hCAP18 (human cationic antimicrobial protein-18), which is produced by neutrophils, keratinocytes, and mucosal epithelial cells. The name refers to the two leucines at the N-terminus and the length of 37 amino acids.

What distinguishes LL-37 from most other peptides in this database is that it is an endogenous human peptide: a compound the body itself produces as part of the first line of defense against infection, rather than a synthetic analog or fragment of a growth hormone. This gives it a unique scientific profile: direct human physiological context is available that is absent for purely synthetic peptides.

The biological functions of LL-37 are remarkably broad. Beyond direct antimicrobial activity against bacteria, fungi, and viruses, it modulates the immune response, promotes angiogenesis, and plays a demonstrated role in wound healing. In chronic wounds, such as diabetic ulcers, LL-37 levels are significantly reduced, and restoration of LL-37 expression is associated with improved re-epithelialization. This is one of the stronger clinical observations available for a research peptide.

The profile of LL-37 also has a complex side. The peptide has dual-sided effects: it can both promote and inhibit inflammation depending on context, concentration, and cell type. In certain circumstances, elevated LL-37 expression is associated with inflammatory skin conditions such as rosacea and psoriasis. This nuanced picture makes LL-37 a scientifically interesting but also complex research subject.

Mechanism of action

LL-37 exerts antimicrobial effects through integration into and disruption of microbial membranes via an amphipathic helix structure, and modulates immune responses via receptor-dependent interactions with host cells.

Antimicrobial membrane disruption

• Amphipathic helix structure makes the peptide soluble in aqueous environments and simultaneously active in lipid-rich membranes
• Forms pores in bacterial cell membranes via toroidal or barrel-stave pore structures
• Broad spectrum: active against gram-positive and gram-negative bacteria, fungi, and some viruses

Immune modulation via receptor signaling

• Modulates TLR-4 signaling through LPS binding, which reduces endotoxin-mediated inflammatory activation
• Stimulates chemotaxis of neutrophils, monocytes, and T cells via FPRL1 receptor
• Induces cytokine production in immune cells, context-dependent pro- or anti-inflammatory

Wound healing and angiogenesis

• Stimulates proliferation and migration of keratinocytes, essential for re-epithelialization
• Promotes angiogenesis via induction of VEGF and direct effects on endothelial cells
• LL-37 levels are significantly elevated in the first 48 hours after skin wounds in vivo

Research findings

• LL-37 is demonstrably present in high concentrations in healing skin wounds in humans in vivo, with peak values at 48 hours post-injury, and significantly reduced in chronic ulcers that fail to heal
• Blocking LL-37 with antibodies inhibits re-epithelialization in an ex vivo human skin model in a concentration-dependent manner. This is direct evidence for the causal role of LL-37 in wound healing
• LL-37 has demonstrated broad antimicrobial activity in multiple studies, including against resistant bacterial strains
• Engineered exosomes loaded with LL-37 showed bactericidal activity, promotion of endothelial cell tube formation, and enhancement of skin cell proliferation and migration in vitro
• In rosacea patients, elevated LL-37 levels are documented as a contributing factor to inflammatory and vascular manifestations, an example of the dual-sided nature of this peptide

In vitro findings

• Broad antimicrobial activity against bacteria, fungi, and viruses
• Stimulation of keratinocyte proliferation and migration
• Induction of angiogenesis via VEGF and endothelial cell activation
• Modulation of NF-kB and TLR signaling in immune cells

Ex vivo and animal model findings

• Blocking LL-37 inhibits re-epithelialization in ex vivo human skin model
• Elevated LL-37 expression in healing wound epithelium in vivo
• Reduced LL-37 levels in chronic ulcers associated with poor wound healing

Human observational data

• LL-37 levels measured in vivo in human skin wounds, with peak values at 48 hours
• Reduced LL-37 in chronic wounds and atopic dermatitis associated with diminished resistance
• Elevated LL-37 in rosacea and psoriasis associated with inflammatory pathology
• LL-37 is an endogenous human peptide; physiological context is directly available

Research context

LL-37 has a stronger human physiological framework than virtually all other peptides in this database. It is an endogenous human peptide with a documented role in wound healing in humans in vivo. The observation that chronic wounds are deficient in LL-37, combined with the direct ex vivo evidence that blocking LL-37 inhibits healing, provides a stronger causal basis than is available for most research peptides.

At the same time, LL-37 illustrates the importance of context in biological activity. The same peptide that promotes wound healing and fights infection contributes in other contexts to inflammatory skin conditions. This makes straightforward interpretations of the literature risky: the concentration, cell type, microbiological context, and route of administration all co-determine which effect dominates.

Exogenous administration of LL-37 for therapeutic purposes in humans has not yet been systematically investigated in controlled trials. The available data are predominantly observational and mechanistic. The step from endogenous physiology to exogenous therapeutic use requires its own pharmacological characterization.

Open questions

LL-37 has the strongest human physiological basis of all regenerative peptides in this database. The distance to therapeutic application via exogenous administration remains large, however: the observational basis is strong, the interventional basis is missing.

• No controlled human intervention studies with exogenous LL-37 available
• Optimal dosing, route of administration, and pharmacokinetics for exogenous use in humans entirely unknown
• Dual-sided effects on inflammation are context-dependent and not fully predictable
• Long-term safety profile for exogenous use not established
• Possible role in cancer development via IGF-1R signaling deserves careful monitoring
• Translation of wound healing data to standardized therapeutic protocols not yet performed

Research outlook

First clinical trials with locally administered LL-37 in chronic wounds are the most logical next step

Controlled release via nanoparticles or exosomes may better steer the dual-sided effects

LL-37 as a biomarker for wound healing prognosis and immune status deserves further investigation

Antimicrobial resistance makes host defense peptides like LL-37 an active area for antibiotic alternatives

Scientific interest

Endogenous antimicrobial peptide of human origin

Wound healing and re-epithelialization

Angiogenesis and tissue regeneration

Dual-sided immune modulation in skin conditions

Specifications

References

1. Epithelial antimicrobial peptides in host defense against infection. · Bals R. · Respiratory Research · 2000
2. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. · Heilborn JD, Nilsson MF, Kratz G, et al. · Journal of Investigative Dermatology · 2003
3. Antimicrobial peptides. · Izadpanah A, Gallo RL. · Journal of the American Academy of Dermatology · 2005
4. A comprehensive summary of LL-37, the factotum human cathelicidin peptide. · Vandamme D, Landuyt B, Luyten W, Schoofs L. · Cellular Immunology · 2012
5. The human cathelicidin LL-37 — a pore-forming antibacterial peptide and host-cell modulator. · Xhindoli D, Pacor S, Benincasa M, et al. · Biochimica et Biophysica Acta · 2016
6. Sodium Bituminosulfonate Used to Treat Rosacea Modulates Generation of Inflammatory Mediators by Primary Human Neutrophils. · Schiffmann S, Gunne S, Henke M, et al. · Journal of Inflammation Research · 2021
7. Engineered Exosomes Containing Cathelicidin/LL-37 Exhibit Multiple Biological Functions. · Su Y, Sharma NS, John JV, et al. · Advanced Healthcare Materials · 2022

Availability

In stock · Batch PEP-LL37-2025-01 · HPLC 98.63 % · released 21 Jun 2026

• LL-37 5 mg · product page with price and batch CoA