Ll-37
LL-37: The Only Human Cathelicidin Peptide
The short answer
LL-37 is the only cathelicidin peptide made in the human body, a 37-amino-acid fragment cleaved from the hCAP18 precursor (Vandamme et al., Cellular Immunology 2012). It is membrane-active: a positive charge pulls it toward microbial surfaces, where it disrupts the membrane and kills a broad range of bacteria (Turner et al., Antimicrob Agents Chemother 1998). It does more than kill microbes, acting as a host-defense peptide that signals to immune cells and supports wound repair (De Yang et al., J Exp Med 2000). Human therapeutic data are early: most evidence comes from cell cultures and animal models, with no large completed human dosing trials (Vandamme et al., 2012). This page is research education, not dosing advice.
This page is general educational information, research-use framing only, not medical advice. Any decision about a research compound belongs with a qualified clinician.
What is LL-37?
LL-37 is the only cathelicidin antimicrobial peptide made in the human body, a 37-residue fragment released from the hCAP18 precursor protein (Vandamme et al., Cellular Immunology 2012).
The peptide is encoded by the CAMP gene, which produces the precursor protein hCAP18. Enzymes cleave off the active C-terminal fragment, and the two leading leucine residues give the peptide its "LL" name and 37-residue length (Gennaro and Zanetti, Biopolymers 2000). It is produced by neutrophils and by epithelial cells lining the skin, airway, and gut, where it sits as part of first-line innate immunity (Vandamme et al., 2012). Chemically, it is a cationic, amphipathic alpha-helix with a net charge of about +6 at physiological pH, and that charge is central to how it works (Vandamme et al., 2012).
| Property | Detail | Source |
|---|---|---|
| Peptide class | Only cathelicidin found in humans | Vandamme et al., 2012 |
| Length | 37 amino acids | Vandamme et al., 2012 |
| Precursor | Cleaved from hCAP18 (CAMP gene) | Vandamme et al., 2012 |
| Net charge | About +6 at physiological pH | Vandamme et al., 2012 |
| Structure | Cationic, amphipathic alpha-helix | Vandamme et al., 2012 |
| Main sources | Neutrophils and epithelial cells | Vandamme et al., 2012 |
How does LL-37 work?
LL-37 is membrane-active: its positive charge draws it to the negatively charged surface of microbes, then it inserts into and disrupts the membrane (Turner et al., Antimicrob Agents Chemother 1998).
Because bacterial membranes carry more negative charge than human cell membranes, the cationic peptide is drawn to microbes first. Once bound, the amphipathic helix packs into the membrane and breaks its integrity, which is why laboratory studies report broad activity against many bacteria, with additional reported effects on some fungi and enveloped viruses (Turner et al., 1998; Vandamme et al., 2012). LL-37 can also bind and neutralize lipopolysaccharide, a component of gram-negative bacteria that triggers strong inflammation, which links its direct killing role to its signaling role (Vandamme et al., 2012).
What does LL-37 do besides kill microbes?
Research describes LL-37 as a host-defense peptide that also signals to the immune system, drawing in immune cells and supporting tissue repair (De Yang et al., J Exp Med 2000).
Beyond direct killing, studies report that LL-37 acts as a chemoattractant for neutrophils, monocytes, and T cells through the receptor FPRL1 (also called FPR2), which recruits these cells toward a site of infection (De Yang et al., 2000). Reviews also describe roles in angiogenesis and wound healing (Vandamme et al., 2012). Its effect on inflammation is context dependent: the same peptide can push a response up or down depending on tissue and concentration, and altered cathelicidin activity has been associated with inflammatory skin conditions. In rosacea, abnormal processing of cathelicidin into different peptide forms was reported to promote skin inflammation (Yamasaki et al., Nature Medicine 2007), and in psoriasis LL-37 has been described as a T-cell autoantigen in a large share of patients (Lande et al., Nature Communications 2014). These are associations reported in the literature, not evidence that LL-37 treats any condition.
What does research report about LL-37 dosing?
There is no established human dose for LL-37, because published work is dominated by laboratory concentrations and animal models rather than human dose-finding trials (Vandamme et al., Cellular Immunology 2012).
The ranges below reflect what published studies and commonly studied research protocols report. This is educational, not a prescription or a personal recommendation. In cell studies, antimicrobial activity is commonly reported in the micromolar range, which is a laboratory concentration and not a human dose. For example, laboratory work reported activity against a range of bacteria in that micromolar range, while antifungal potency against Candida albicans was low in the same study (Turner et al., Antimicrob Agents Chemother 1998). No large completed human trial has defined a safe and effective systemic dose, a duration, or a route for LL-37 as a research peptide (Vandamme et al., 2012). For that reason this page does not list a milligram protocol. Anyone considering LL-37 in a research or clinical setting should route dose, route, and monitoring decisions to a qualified clinician.
| Research setting | What is measured | Evidence maturity | Source |
|---|---|---|---|
| In vitro (cell and microbe cultures) | Antimicrobial activity, often in the micromolar range | Most abundant data | Turner et al., 1998 |
| Immune signaling assays | Chemotaxis and receptor activation (FPRL1 / FPR2) | Well described | De Yang et al., 2000 |
| Animal models | Wound repair, host defense, inflammation | Supportive, not human | Vandamme et al., 2012 |
| Human dose-finding | A defined therapeutic dose | No large completed trials | Vandamme et al., 2012 |
Is LL-37 safe, and what side effects are reported?
Human safety is not established for LL-37 because there are no large completed clinical trials, and laboratory research shows the peptide can damage host cells at higher concentrations (Vandamme et al., Cellular Immunology 2012).
The membrane-active property that lets LL-37 break down microbes can also affect human cells, so concentration and context matter. Reviews report that LL-37 can show hemolytic and cytotoxic effects on host cells as the concentration rises (Vandamme et al., 2012). Reviews note that cathelicidin activity can move inflammation in either direction depending on the tissue, and that altered LL-37 levels have been linked to inflammatory skin conditions such as rosacea and psoriasis (Yamasaki et al., 2007; Lande et al., 2014). None of that describes a treatment; it describes patterns reported in the literature. Since human dosing data are early, the side-effect profile for LL-37 as an injectable research compound is not defined, which is why clinician oversight matters.
What is the half-life and pharmacokinetics of LL-37?
Human pharmacokinetic data for LL-37 are limited, and no large clinical study has published a validated systemic half-life for the peptide as a research compound (Vandamme et al., Cellular Immunology 2012).
Like many peptides, LL-37 is subject to enzymatic breakdown, and its activity in the body is also shaped by binding to other molecules. Reviews note that serum components can inhibit its antimicrobial action, which is one reason laboratory potency does not translate directly to a systemic dose (Vandamme et al., 2012). Because a validated human half-life is not established, any pharmacokinetic figure quoted for LL-37 should be treated as preliminary and read against the source it came from.
What does vitamin D have to do with LL-37?
Vitamin D signaling can raise expression of the CAMP gene that produces LL-37, which is a well-documented molecular link (Gombart et al., FASEB J 2005).
The CAMP gene carries a vitamin D response element in its promoter, and 1,25-dihydroxyvitamin D3 (the active form of vitamin D) acts through the vitamin D receptor to increase CAMP expression in myeloid cells (Gombart et al., 2005). This is a mechanism reported at the gene level. It does not mean that taking vitamin D produces a specific clinical effect through LL-37, and it is not dosing advice.
How does LL-37 fit with other immune-family research peptides?
LL-37 is a direct, membrane-active host-defense peptide, which sets it apart from the immune-signaling peptides in the same research family.
Its defining feature in the literature is that it both kills microbes directly and signals to immune cells (Turner et al., 1998; De Yang et al., 2000), while the broader immune-peptide family covers compounds studied mainly for immune modulation and inflammation. Two related hubs are thymosin alpha-1 and KPV, and each has its own mechanism, its own evidence base, and its own page. Because human data across this family are still early, treat each as a research compound and route any protocol to a qualified clinician. For background on peptide classes and how they are studied, see the guide to what peptides are.
Keep reading
Related research and verification
Ll-37: FAQ
References
- Vandamme D, Landuyt B, Luyten W, Schoofs L. A [...] summary of LL-37, the factotum human cathelicidin peptide. Cell Immunol. 2012;280(1):22-35. PMID: 23246832. doi:10.1016/j.cellimm.2012.11.009
- Gennaro R, Zanetti M. Structural features and biological activities of the cathelicidin-derived antimicrobial peptides. Biopolymers. 2000;55(1):31-49. PMID: 10931440
- Turner J, Cho Y, Dinh NN, Waring AJ, Lehrer RI. Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrobial Agents and Chemotherapy. 1998;42(9):2206-2214. PMID: 9736536
- De Yang, Chen Q, Schmidt AP, et al. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. Journal of Experimental Medicine. 2000;192(7):1069-1074. PMID: 11015447
- Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. The FASEB Journal. 2005;19(9):1067-1077. PMID: 15985530
- Yamasaki K, Di Nardo A, Bardan A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nature Medicine. 2007;13(8):975-980. PMID: 17676051
- Lande R, Botti E, Jandus C, et al. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nature Communications. 2014;5:5621. doi:10.1038/ncomms6621
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General educational information only, research-use framing, not medical advice. Confirm the current status where you live and consult a qualified professional before acting.