LL-37

01 · What it is

LL-37 is cytotoxic to human cells, and this is not a side note in its literature — it is a well-replicated property studied on its own terms.

A 2024 study of vitamin D-triggered cathelicidin production states the position plainly: LL-37 shows activity against microorganisms, but it is also cytotoxic to host cells, and the paper’s subject is LL-37-induced human osteoblast cytotoxicity ¹². A 2025 study found that direct stimulation of human colonic epithelial cells with LL-37 produced a rapid and transient increase in epithelial permeability ¹⁴ — the peptide disrupting the barrier it is elsewhere credited with protecting.

And LL-37 is implicated in the pathogenesis of a human autoimmune disease. In psoriasis, cathelicidin is among the antimicrobial peptides secreted into lesional skin that activate innate immunity and induce inflammation, participating in the disease process rather than resolving it ⁵.

What it is. LL-37 is the only member of the cathelicidin family of host-defence peptides expressed in humans ¹ — the C-terminal peptide of human cathelicidin antimicrobial protein, hCAP18 ³. It is genuinely endogenous, produced by phagocytic leukocytes and epithelial cells ¹⁵, and it has become a paradigm for the pleiotropic roles peptides play in host defence ².

Its mechanism is membrane disruption, and that is the problem. LL-37 is described as a pore-forming antibacterial peptide and host-cell modulator ². A molecule that kills bacteria by permeabilising membranes does not stop at bacterial membranes, which is the mechanistic reason the cytotoxicity findings above are what one should expect rather than a surprise.

The literature is enormous and it is almost entirely about endogenous LL-37. Nearly two thousand records match a broad search. Reviews cover antifungal activity ⁸, antibiofilm properties ⁶, roles in cancer ³, TLR modulation ⁴, periodontitis ¹⁵ and wound healing ¹⁹. What this guide did not locate is a clinical trial in which LL-37 was administered to people.

LL-37 is one of the best-characterised molecules in this project and among the least suitable for casual administration, for reasons its own literature documents in detail.

02 · Evidence at a glance

Evidence grade

Preclinical — no trial of administered LL-37 located

What it is

The sole human cathelicidin; C-terminal peptide of hCAP18 ^1,3

Where it comes from

Phagocytic leukocytes and epithelial cells ¹⁵

Mechanism

Pore formation and membrane disruption, plus host-cell modulation ²

Cytotoxic to human cells

Yes — documented, including human osteoblasts ¹²

Effect on human colonic epithelium

Rapid, transient increase in permeability — barrier disruption ¹⁴

Role in human disease

Implicated in the pathogenesis of psoriasis ⁵

Nucleic acid binding

Forms complexes with nucleic acids with beneficial or detrimental effects ¹⁰; compacts DNA and alters neutrophil extracellular trap structure ²⁰

Role in cancer

Reviewed as bidirectional ³

Stability

Low activity and instability in physiological environments ¹³

Reported benefits, animal and cell

Diabetic wound healing in mice ⁹; intestinal barrier in heat-stroke rats ⁷; LDL clearance ¹⁸; antifungal ⁸; antibiofilm ⁶

Human trials of administered LL-37

None located

Human safety data from administration

None

Literature size

~1,927 records on a broad search — the largest in this project

US regulatory status

Not an approved drug; not a lawful dietary supplement ingredient

03 · Mechanism of action

A pore-forming peptide

LL-37 is characterised as a pore-forming antibacterial peptide and host-cell modulator with a remarkably wide functional repertoire: direct antimicrobial activity against various microorganisms, plus roles that extend well past killing bacteria ².

Membrane permeabilisation is not a targeted mechanism. It is selective for bacterial membranes by degree — lipid composition and charge — not by kind, and the cytotoxicity literature is what that degree of selectivity looks like when measured in human cells ^12,14.

The immunomodulatory half

Beyond direct antimicrobial action, LL-37 modulates Toll-like receptor activation and inflammation through both direct peptide–ligand interactions — altering ligand stability, cellular uptake and receptor interaction — and indirect mechanisms ⁴. It has documented roles in chemotaxis, promotion of wound closure and angiogenesis ³, and interacts synergistically and antagonistically with other immune mediators ¹.

This is the half that makes LL-37 interesting as a therapeutic and also the half that makes its effects hard to predict: a molecule that alters how other immune signals are received will do different things depending on what else is happening.

Nucleic acid complexation, and why it matters

LL-37 forms complexes with nucleic acids, and the literature is explicit that these can have either beneficial or detrimental health effects ¹⁰. It compacts nucleic acids and alters the structure of neutrophil extracellular traps ²⁰.

This is the mechanistic bridge to autoimmunity. A peptide that binds host DNA and changes how it is presented is the kind of molecule that can convert self-material into an immune stimulus, and psoriasis ⁵ is where that shows up clinically.

The instability problem

Human LL-37 offers significant benefits to the immune system and in treating various diseases, but its therapeutic potential is hindered by low activity and instability in physiological environments ¹³. That assessment comes from a paper building a delivery system to work around it, and a 2025 review describes a wide range of design strategies employed to overcome the challenges of the native peptide ¹⁶.

As with KPV elsewhere in this family, a substantial part of the modern literature exists to fix the molecule rather than to use it. Synthetic analogues — ceragenins — are being developed for wound healing precisely because the natural peptide is difficult ¹⁹.

04 · Key research findings

Characterisation as the sole human cathelicidin, 2009. A review establishing LL-37 as the only member of the cathelicidin family of host-defence peptides expressed in humans, and setting out its synergistic and antagonistic interactions with other immune mediators ¹.

The pore-forming paradigm, 2016. A review of hCAP18/LL-37 as a paradigm for pleiotropic peptide roles in host defence, covering direct antimicrobial activity and host-cell modulation ².

Cancer, 2018. A review of roles and mechanisms in cancer, noting that LL-37 increases resistance to microbial invasion and has physiological functions in chemotaxis, wound closure and angiogenesis ³.

Chemotaxis, wound closure and angiogenesis are the same processes tumours use. A review of LL-37 in cancer exists because the direction of effect is not settled.

Psoriasis, 2020. A review of antimicrobial peptides in psoriasis describing cathelicidin among the peptides secreted in lesional skin that activate the innate immune system and induce inflammation, thereby participating in the pathogenesis of the disease ⁵.

The single most important paper in this file for anyone considering exposure. LL-37 is not hypothesised to cause psoriasis-like inflammation; it is described in the dermatology literature as part of how psoriasis works.

Antimicrobial breadth, 2023. In-depth reviews of antibiofilm properties ⁶ and antifungal properties ⁸, the latter noting an explosion of knowledge on the microbicidal activity of the sole human cathelicidin.

Heat stroke in rats, 2023. LL-37 reported to preserve intestinal barrier and organ function in Wistar rats subjected to a 42 °C heating chamber ⁷.

Breast implant capsules, 2024. LL-37 expression examined in human capsular tissue in the context of capsular contracture, the most common complication of breast implant placement ¹⁰.

An observational human tissue study of endogenous expression, not administration.

Diabetic wound healing in mice, 2024. LL-37 reported to promote wound healing in diabetic mice via TFEB-dependent autophagy, with TFEB knockdown impairing the effect ⁹.

One of the cleanest positive animal results in the file, with a mechanism tested by knockdown.

Nucleic acid complexation, 2024 and 2026. A review titled around the dual nature of LL-37–nucleic acid complexes ¹¹, and a study showing the peptide compacts nucleic acids and alters neutrophil extracellular trap structure ²⁰.

Osteoblast cytotoxicity, 2024. Vitamin D triggers hCAP18/LL-37 production, and the paper’s subject is the implication of that for LL-37-induced human osteoblast cytotoxicity. The concentration reached in vitamin D-stimulated THP-1 cells corresponds to 1.04 μM LL-37 ¹².

A concentration figure tied to a physiological stimulus, in a paper about the peptide harming a human cell type. That combination is rare and useful.

Instability and delivery, 2025. A study reporting that LL-37’s therapeutic potential is hindered by low activity and instability in physiological environments, using prolonged immunomodulator delivery to boost monocyte exosome secretion and elevate cathelicidin content ¹³.

Colonic epithelial disruption, 2025. Direct stimulation of human colonic epithelial T84 cells with LL-37 produced a rapid and transient increase in epithelial cell permeability ¹⁴.

Set beside the heat-stroke result where LL-37 preserved intestinal barrier function in rats ⁷, this is a direct conflict in the same organ system between species and model. Neither paper resolves it and this guide does not either.

Mucus barrier regulation, 2025. Work in cathelicidin-deficient mice, colonoids and human goblet-like cells examining regulation of goblet cell mucus secretion during Citrobacter rodentium colitis ¹⁷.

A knockout study — the cleanest way to ask what endogenous cathelicidin does, and a different question from what administering it would do.

Analogue development, 2025 and 2026. A review of design strategies to overcome the native peptide’s limitations ¹⁶, and a review of LL-37 and its synthetic ceragenin analogues in wound healing, describing ceragenins as promising candidates ¹⁹.

LDL and liver cholesterol, 2026. LL-37 reported to bind LDL via ApoB-100 domains, enhancing ApoB-100 solubility, inhibiting LDL modification and aggregation, and promoting LDL clearance ¹⁸.

A genuinely new direction, published in 2026, and an illustration of how far this molecule’s documented interactions extend beyond immunity.

05 · Evidence overview

06 · Safety profile

This is the rare compound in this project whose harms are better documented than its benefits, and the reason is that its harms are being studied as biology rather than as adverse events.

Cytotoxicity. LL-37 is cytotoxic to host cells, and human osteoblast cytotoxicity has been studied directly, at concentrations reached when cells are stimulated with vitamin D — around 1.04 μM in the model used ¹².

Barrier disruption. Direct application to human colonic epithelial cells rapidly increased permeability ¹⁴.

Autoimmune involvement. Cathelicidin is described in the dermatology literature as participating in the pathogenesis of psoriasis through innate immune activation in lesional skin ⁵, and the molecular route — complexation with host nucleic acids, with effects the literature describes as beneficial or detrimental ¹⁰ and including altered neutrophil extracellular trap structure ²⁰ — is precisely the kind of mechanism that turns self-material into an immune stimulus.

Oncological uncertainty. A dedicated review exists on roles and mechanisms in cancer ³, and the functions attributed to LL-37 — chemotaxis, wound closure, angiogenesis — are functions tumours exploit. The direction of effect is not established.

What is genuinely unknown. Everything about administration. No human pharmacokinetics, no dose-finding, no repeat-dose toxicology, no route comparison. Given documented cytotoxicity at low-micromolar concentrations ¹², the absence of any dose-ranging study is the central gap rather than a technicality: there is no published basis for identifying a concentration that is antimicrobial without being cytotoxic in a person.

Also unknown: what administration does in anyone with psoriasis or another autoimmune condition, given the pathogenic role ⁵; whether the protective gut findings in rats ⁷ or the disruptive findings in human cells ¹⁴ better predict what happens in a person; and the identity and purity of any material sold under this name, on which nothing is published.

07 · US regulatory status

Current as of 7 September 2026. LL-37 is not an approved drug in the United States, is not a controlled substance, and is not a lawful dietary supplement ingredient. No marketing authorisation in any jurisdiction was identified for this guide.

Under the World Anti-Doping Code, LL-37 does not appear as a named prohibited substance in the classes reviewed here. Competitors should consult the current Prohibited List directly rather than rely on secondary summaries, including this one.

08 · Limitations of the evidence

1. The enormous literature is about endogenous LL-37, not administered LL-37. Roughly 1,927 records, and this guide located no clinical trial of the peptide as a treatment. Studies of what a molecule does when the body makes it do not establish what happens when it is supplied from outside, at an unregulated dose, by an unstudied route.
2. Cytotoxicity to human cells is documented, not theoretical ¹². Any claim about benefit has to be set against a property the compound’s own literature describes as intrinsic to how it works ².
3. It participates in the pathogenesis of a human autoimmune disease ⁵. This is the most consequential single fact in the guide and it comes from mainstream dermatology, not from adverse event reporting.
4. Findings on the gut barrier point in opposite directions. Protective in heat-stroke rats ⁷; permeability-increasing in human colonic epithelial cells ¹⁴. Species, model and route all differ, and nothing located here reconciles them.
5. The direction of effect in cancer is unresolved ³, in a molecule with documented pro-angiogenic and chemotactic activity.
6. The native peptide is unstable and weakly active in physiological conditions ^13,16, which means results obtained with engineered analogues or delivery systems ^13,19 do not transfer to plain peptide.
7. No dose has ever been established for human use, while cytotoxicity is reported at low-micromolar concentrations ¹². There is no published therapeutic window.
8. Animal-to-human translation is unattempted, and the animal models — heat stroke ⁷, diabetic wounds ⁹, Citrobacter colitis ¹⁷ — are acute induced-injury models.
9. Publication bias cannot be assessed in a literature this large and this heterogeneous, though the presence of prominent negative and cautionary findings ^5,12,14 suggests the field is not suppressing them.
10. This guide has read abstracts, not full texts, for every source cited, in a literature where fewer than twenty of nearly two thousand records were examined. The selection here is weighted toward reviews and toward the safety-relevant primary studies, and a different selection would emphasise different things — that choice is disclosed rather than hidden.
11. Nothing is known about material sold under this name. No published analysis has examined the identity or purity of any LL-37-labelled product.

09 · References

1. Nijnik A, Hancock RE. The roles of cathelicidin LL-37 in immune defences and novel clinical applications. Curr Opin Hematol. 2009 Jan;16(1):41–47. Review.

   PMID 19068548 ↗

2. Xhindoli D, Pacor S, Benincasa M, Scocchi M, Gennaro R, Tossi A. The human cathelicidin LL-37 — a pore-forming antibacterial peptide and host-cell modulator. Biochim Biophys Acta. 2016 Mar;1858(3):546–566. Review.

   PMID 26556394 ↗

3. Chen X, Zou X, Qi G, Tang Y, Guo Y, Si J, Liang L. Roles and mechanisms of human cathelicidin LL-37 in cancer. Cell Physiol Biochem. 2018;47(3):1060–1073. Review.

   PMID 29843147 ↗

4. Scheenstra MR, van Harten RM, Veldhuizen EJA, Haagsman HP, Coorens M. Cathelicidins modulate TLR-activation and inflammation. Front Immunol. 2020 Jun 9;11:1137. Review.

   PMID 32582207 ↗

5. Takahashi T, Yamasaki K. Psoriasis and antimicrobial peptides. Int J Mol Sci. 2020 Sep 16;21(18):6791. Review.

   PMID 32947991 ↗

6. Memariani H, Memariani M. Antibiofilm properties of cathelicidin LL-37: an in-depth review. World J Microbiol Biotechnol. 2023 Feb 14;39(4):99. Review.

   PMID 36781570 ↗

7. Shih CC, Liao WC, Ke HY, Kuo CW, Tsao CM, Tsai WC, Chiu YL, Huang HC, Wu CC. Antimicrobial peptide cathelicidin LL-37 preserves intestinal barrier and organ function in rats with heat stroke. Biomed Pharmacother. 2023 May;161:114565.

   PMID 36958193 ↗

8. Memariani M, Memariani H. Antifungal properties of cathelicidin LL-37: current knowledge and future research directions. World J Microbiol Biotechnol. 2023 Dec 7;40(1):34. Review.

   PMID 38057654 ↗

9. Xi L, Du J, Xue W, Shao K, Jiang X, Peng W, Li W, Huang S. Cathelicidin LL-37 promotes wound healing in diabetic mice by regulating TFEB-dependent autophagy. Peptides. 2024 May;175:171183.

   PMID 38423213 ↗

10. Segreto F, Carotti S, Marangi GF, Francesconi M, Calia E, Cagli B, Cimmino A, Rossi C, Morini S, Persichetti P. Cathelicidin LL-37 expression in human breast implant capsules. Plast Reconstr Surg. 2024 May 1;153(5):1066–1073.

    PMID 37220260 ↗

11. Zielke C, Nielsen JE, Lin JS, Barron AE. Between good and evil: complexation of the human cathelicidin LL-37 with nucleic acids. Biophys J. 2024 Jun 4;123(11):1316–1328. Review.

    PMID 37919905 ↗

12. Aidoukovitch A, Bankell E, Svensson D, Nilsson BO. Vitamin D triggers hCAP18/LL-37 production: implications for LL-37-induced human osteoblast cytotoxicity. Biochem Biophys Res Commun. 2024 Jun 18;712–713:149962.

    PMID 38642493 ↗

13. Ma D, Su Y, Sharma NS, Hatcher G, Ganguli-Indra G, Indra AK, Gombart AF, Xie J. Prolonged immunomodulator delivery boosts monocyte exosome secretion and elevates cathelicidin/LL-37 content. ACS Appl Mater Interfaces. 2025 Jan 8;17(1):799–810.

    PMID 39700070 ↗

14. Kilari G, Tran J, Blyth GAD, Cobo ER. Human cathelicidin LL-37 rapidly disrupted colonic epithelial integrity. Biochim Biophys Acta Biomembr. 2025 Mar;1867(3):184410.

    PMID 39837472 ↗

15. He Y, Zhou Y, Liu N, Zhang W, Chen X, Qiu G, Shen Y. Cathelicidin LL-37 in periodontitis: current research advances and future prospects — a review. Int Immunopharmacol. 2025 Mar 26;150:114277. Review.

    PMID 39954662 ↗

16. Voronko OE, Khotina VA, Kashirskikh DA, Lee AA, Gasanov VAO. Antimicrobial peptides of the cathelicidin family: focus on LL-37 and its modifications. Int J Mol Sci. 2025 Aug 21;26(16):8103. Review.

    PMID 40869425 ↗

17. Mirzadzare N, Blyth GAD, Hannawayya R, Cirone KM, Kilari G, Lahiri P, Tan YL, Herik AI, Fu Y, Gorman H, Petri B, Chadee K, Cobo ER. Cathelicidin regulates goblet cell mucus secretion and mucus-associated proteins in Citrobacter rodentium-induced colitis. Gut Microbes. 2025 Dec;17(1):2538696.

    PMID 40735968 ↗

18. Fang Y, Zhang Z, Cao Q, Wang G, Duan Z, Meng P, Zhou S, Fei S, Tadese DA, Mwangi J, Lu Q, Ni H, Lai R. Cathelicidin LL-37-ApoB-100 interaction promotes LDL clearance and attenuates cholesterol accumulation in the liver. Sci China Life Sci. 2026 Feb;69(2):492–505.

    PMID 40971038 ↗

19. Łuckiewicz M, Wnorowska U, Zakrzewska M, Błażejczyk I, Daniluk T, Kondziołka W, Savage PB, Bucki R, Piktel E. Exploring the role of cathelicidin LL-37 and ceragenins in wound healing processes. Eur J Pharmacol. 2026 Mar 28;1019:178727. Review.

    PMID 41791569 ↗

20. Zielke C, Rad B, Nielsen JE, Li J, Pimcharoen S, Sawant M, Kamayirese S, Lin JS, Thiam HR, Barron AE. Human cathelicidin peptide LL-37 compacts nucleic acids and alters neutrophil extracellular trap structure. Sci Rep. 2026 May 19;16(1):22524.

    PMID 42156793 ↗