Last Updated January 18, 2024

 January 18, 2024

Research professionals specializing in immunity research may be interested in determining a proper LL-37 dosage for their experiments.

LL-37 is an endogenous peptide that is integral to the human immune response. This peptide, synthesized in response to injury or infection, plays a pivotal role in modulating immune functions and accelerating wound healing.

According to studies published so far, LL-37's potential benefits include:

  • Immune Function Modulation
  • Accelerated Wound Healing
  • Antimicrobial Activity

This expert guide provides a comprehensive analysis of LL-37's biological functions, therapeutic applications, and a systematic approach for determining optimal dosages.

Below, researchers can find a detailed dosing calculator and chart to suit a diverse range of experimental needs.

Buy LL-37 from our top-rated vendor...

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LL-37 Dosage Chart | Quick Breakdown

Time frame Daily LL-37 Dosage for Immunomodulation Research
Week 1-4 125mcg/daily, s.c.
Week 5-6 Washout (Pause)
Week 7-10 125mcg/daily, s.c.
Week 11-12 Washout

What is LL-37?

LL-37 (CAP-18) is an endogenous peptide and is categorized as an antimicrobial peptide (AMP). There are two main families of AMPs: defensins and cathelicidins [1]

LL-37 is the only human member of the cathelicidin family of antimicrobial peptides. It is made up of 37 amino acids and comes from a larger protein called the human cathelicidin antimicrobial protein.

Due to its importance for immune defense, LL-37 is expressed in a wide range of tissues including in the majority of immune cells, epithelial cells of the testis, skin, gastrointestinal tract, and respiratory tract.

The peptide is specifically expressed in leukocytes such as monocytes, neutrophils, T-lymphocytes, Natural Killer (NK) cells, and B-lymphocytes. Research also suggests additional defensive roles of LL-37, including [2, 3]:

  • regulating the inflammatory response
  • attracting cells of the adaptive immune system (such as CD4 T lymphocytes) to wound or infection sites
  • binding and neutralizing foreign molecules such as bacterial toxins
  • promoting re-epithelialization and wound closure

LL-37 is stimulated in cases of infection, injuries, UV irradiation, and the disruption of different barriers in the body.

Studies also suggest that one of the main ways by which the body regulates the expression of LL-37 in different cell types is via vitamin D-dependent mechanisms. Thus, vitamin D status may impact the LL-37 response in any of the aforementioned cases [4].

Currently, researchers are actively investigating the potential of LL-37 in various cell lines and in vitro models, and the peptide is available as a reference material for laboratory experiments. It is currently not approved for human or animal use due to lack of preclinical and clinical review.


LL-37 Dosage Calculator


Research Application and Potential Benefits of LL-37

LL-37 is a unique peptide that is integral to the human immune response. It has been the focus of numerous preclinical studies and a limited number of clinical trials.

Here are some of the more notable potential benefits of this peptide based on the available research.

Bactericidal Action of LL-37

Preliminary experiments have reported that LL-37 appears to have potent bactericidal effects on a wide range of pathogens, including but not limited to [5, 6, 7, 8]:

  • Helicobacter pylori
  • Escherichia coli
  • Staphylococcus aureus
  • Pseudomonas aeruginosa

While clinical trials on the bactericidal action of LL-37 are lacking, preclinical studies reveal that the peptide has protective effects in various models of infection:

  • One study investigated LL-37's efficacy against sepsis (generalized infection) in rats treated intravenously with isotonic sodium chloride, LL-37, or three different antibiotics. All treatments reduced lethality, and LL-37 was comparable in effectiveness to the antibiotics but resulted in significantly lower endotoxin and inflammation levels [9].
  • In another murine sepsis study, LL-37 enhanced the survival of septic mice by inhibiting macrophage pyroptosis (a form of cell death that is triggered by proinflammatory signals and associated with inflammation), thereby reducing inflammation. LL-37 also stimulated neutrophils to release antimicrobial microvesicles (ectosomes), further protecting against sepsis [10].
  • A study examining the effects of LL-37 on mice with gastrointestinal Escherichia coli infection demonstrated the peptide’s protective properties. LL-37 reduced body weight loss, intestinal damage, and epithelial apoptosis. It also decreased inflammatory infiltration in the jejunum and colon and downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) while upregulating anti-inflammatory cytokine IL-10 [11].

LL-37 and Immune System Modulation

LL-37 has been reported to influence the immune system and its potential to defend against both bacterial and viral threats. Here are some of the most notable trials on the topic.

  • One experiment reported that LL-37 plays a role in boosting the body's immune response to double-stranded RNA molecules (dsRNA), which are the main form of genetic material in several types of viruses, such as rotaviruses. This enhanced immune response mechanism could lead to a more effective defense against viral infections [12].
  • Another study explored the effect of LL-37 on mast cell activation, a crucial aspect of the body's defense against bacteria. LL-37 acts as a potent chemoattractant for mast cells and directly stimulates them, causing degranulation and the production of pro-inflammatory cytokines [13].

LL-37 and Wound Healing

LL-37 is under investigation for its potential in wound healing, with clinical trials having shown benefits following its topical application on injuries:

  • In a clinical trial with 34 participants, LL-37 was tested on hard-to-heal venous leg ulcers. Over 4 weeks, participants received twice-weekly topical doses of 0.5, 1.6, or 3.2 mg/mL LL-37 or placebo. Significant healing improvements were noted in the 0.5 and 1.6 mg/mL groups, with ulcer size reductions of 68% and 50%, respectively [14].
  • Another study included 18 participants receiving LL-37 cream or placebo twice weekly for 4 weeks. The LL-37 group showed a consistently greater increase in the formation of new tissue and blood vessels and a tendency for reduced bacterial colonization [15].
  • A phase 2b clinical trial called HEAL evaluated the safety and efficacy of topical LL-37 at concentrations of 0.5 or 1.6 mg/mL in conjunction with compression therapy in 148 patients with hard-to-heal venous leg ulcers. After four weeks of therapy, the researchers observed a significant benefit in patients with larger ulcers (over 10 cm²). The treatment was deemed safe and well-tolerated [16].

Side Effects of LL-37

LL-37 has been clinically studied for its safety and efficacy in the form of topical creams and oral capsules:

  • In a phase 2b clinical trial, LL-37 showed excellent safety and a low risk of side effects. Only some of the adverse events, such as infection at the site of the wound, phlebitis, and peripheral swelling, were judged as potentially related to its administration [16].
  • Oral LL-37 was tested in one trial in 238 participants infected with the Omicron BA.5.1.3 variant of SARS-COV-2. The authors did not report any serious adverse events or safety concerns [17].

Unfortunately, clinical studies on injectable LL-37 safety are lacking. Preliminary experiments report that LL-37 may target pathogens such as bacteria even when administered at concentrations that do not exert any toxicity on healthy cells [18].

However, some trials have also raised concerns that LL-37 is overexpressed in various pathological conditions such as chronic inflammation (e.g., COPD, cystic fibrosis, etc), autoimmune diseases (e.g. psoriasis) and even some types of cancer [19, 20].

For example, studies in COPD and cystic fibrosis report that LL-37 is associated with increased inflammation, mucus production, and fibrosis [21, 22, 23, 24].

Further, LL-37 has been reported to promote cancer progression in ovarian tumor cell cultures. Yet, at the same time, it appears to exert anti-tumor activity in colon cancer cell lines [20].

Overall, topical LL-37 appears to be safe and well-tolerated. But considering the conflicting evidence and the lack of high-quality studies, researchers cannot draw conclusions on the safety and potential risks of other formats of LL-37 at this time. Thus, more clinical trials are needed to fully elucidate the safety profile of this peptide.


LL-37 Dosage Calculator

Currently, clinical data on LL-37 dosage is available only for its topical application. The studies report that it has been applied successfully on the wounds of volunteers at concentrations of 0.5 and 1.6mg/mL LL-37 per day [16].

While the peptide has also been clinically applied as oral capsules, the sole clinical trial involving such a formulation has not disclosed the specific doses administered to the participants [17].

On the other hand, the available preclinical studies have used up to 1mg/kg/daily LL-37 on rats and 5mg/kg/daily LL-37 on mice with great effectiveness against various pathogens. Yet, these concentrations cannot be directly extrapolated to humans [9, 10].

Anecdotal reports have suggested that the peptide may be applied at doses of 125mcg/daily, and the most convenient method of administration may be subcutaneous injections (s.c.).

Researchers should note that there is no scientific data to support the safety or effectiveness of such suggestions.


Microdosing LL-37?

Microdosing is the method of applying a compound at doses significantly below therapeutic levels, with the hope of still achieving some potential benefits while completely avoiding risks and side effects.

This has become a popular idea with psychedelics, but some researchers have also considered it as a strategy for the application of experimental research compounds such as peptides.

Currently, there is no evidence suggesting that microdosing LL-37 may be effective and provide any benefits in any type of setting. Researchers have yet to determine the proper dose of LL-37 for use in clinical settings to potentially estimate the correct amount to be used for microdosing.


LL-37 Cycle Length?

Available clinical data reveals that LL-37 has been applied topically for up to four weeks, during which the peptide has exerted significant benefits for wound healing [25]. It has also been clinically applied as oral capsules for up to seven days [26].

Preclinical experiments have used LL-37 for the management of severe infections for up to five days [10]. Yet, clinical data on the injectable administration of LL-37 is lacking.


How to Reconstitute LL-37

LL-37 as a reference material for experimentation is typically supplied in the form of lyophilized (freeze-dried) powder.

Freeze-dried peptides are also known as “raw” peptides and must first be reconstituted into a liquid with a suitable solvent before being used in research.

Most peptides, including LL-37, are best reconstituted with bacteriostatic water. This solvent contains sterile water for injections and 0.9% benzyl alcohol as a preservative, which prevents bacterial contamination and prolongs the shelf life of the peptide.

Peptides reconstituted with bacteriostatic water remain safe and viable for research for 28 days when refrigerated at temperatures between 36-46°F.

Researchers are recommended to obtain bacteriostatic water from a reputable and trusted vendor. In addition, researchers must also obtain:

  • Sterile syringes
  • Sterile needle
  • Alcohol pads for sterilization
  • A container designated for sharp object disposal

Here is a step-by-step process that researchers typically follow to successfully reconstitute LL-37 peptide for experimentation:

  • Use alcohol pads to sterilize the stoppers of both the LL-37 peptide and the bacteriostatic water vial.
  • Then, attach the sterile needle to the syringe and withdraw the correct amount of solvent from the bacteriostatic water vial.
  • Insert the needle into the peptide vial and slowly spray the solvent while directing the stream toward the wall of the vial to prevent foaming.
  • Once the solvent is mixed with the peptide, the powder should dissolve on its own.

The peptide vial should not be shaken or tapped, as such mechanical forces can damage its structure and render it inactive. LL-37 peptide can also get damaged if refrigerated, heated, or exposed to direct sunlight.


LL-37 Dosage Calculator


Where to Buy LL-37 Online? | 2024 Edition

LL-37 is available for online purchase by qualified researchers and laboratory professionals.

To ensure validity in their experimentation, researchers will need to identify a credible provider of high-quality research peptides.

At Peptides.org, we’re proud to recommend the following esteemed provider of LL-37 and a range of research peptides.

Limitless Life

We trust Limitless Life for the following reasons:

  • Exceptional Purity Standards: Limitless Life prides itself on delivering LL-37 at a 99% purity level, minimizing the presence of contaminants and fillers. Their assurance is backed by third-party party testing.
  • Perks & Promotions: Peptide research is costly, but Limitless Life provides a variety of cost-saving benefits like free shipping on orders of $100+ and a 10% discount for first-time newsletter subscribers.
  • Responsive Customer Support: Limitless Life excels in customer service, offering prompt and efficient responses to inquiries by phone and email. Their approachable and knowledgeable team fosters a sense of trust and loyalty among buyers.
  • Streamlined Purchasing Process: The simplicity of Limitless Life’s website and range of payments accepted ensure hassle-free transactions.

Limitless Life is a leading choice for research peptides like LL-37, thanks to its commitments to product purity, customer satisfaction, and overall excellence.

Buy LL-37 from our top-rated vendor...


LL-37 Dosing Guide | Verdict

LL-37 is an endogenous peptide and promising research chemical that is under investigation for a range of potential benefits, including in the management of various infections and the healing of infected or hard-to-heal wounds.

As a therapeutic for wound healing, the peptide has been successfully dosed as a topical formulation in doses ranging between 0.5 and 1.6 mg/mL.

Yet, the majority of studies investigating LL-37’s potential for the management of infections and modulating the immune system are preliminary, and specific dosages for LL-37 are yet to be determined.

Researchers interested in conducting research with LL-37 should visit our #1 preferred online vendor.


References

  1. Ridyard, K. E., & Overhage, J. (2021). The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent. Antibiotics (Basel, Switzerland), 10(6), 650. https://doi.org/10.3390/antibiotics10060650
  2. Agerberth, B., Charo, J., Werr, J., Olsson, B., Idali, F., Lindbom, L., Kiessling, R., Jörnvall, H., Wigzell, H., & Gudmundsson, G. H. (2000). The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood, 96(9), 3086–3093.
  3. Dürr, U. H., Sudheendra, U. S., & Ramamoorthy, A. (2006). LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochimica et biophysica acta, 1758(9), 1408–1425. https://doi.org/10.1016/j.bbamem.2006.03.030
  4. Park, K., Elias, P. M., Oda, Y., Mackenzie, D., Mauro, T., Holleran, W. M., & Uchida, Y. (2011). Regulation of cathelicidin antimicrobial peptide expression by an endoplasmic reticulum (ER) stress signaling, vitamin D receptor-independent pathway. The Journal of biological chemistry, 286(39), 34121–34130. https://doi.org/10.1074/jbc.M111.250431
  5. Hase, K., Murakami, M., Iimura, M., Cole, S. P., Horibe, Y., Ohtake, T., Obonyo, M., Gallo, R. L., Eckmann, L., & Kagnoff, M. F. (2003). Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. Gastroenterology, 125(6), 1613–1625. https://doi.org/10.1053/j.gastro.2003.08.028
  6. Johansson, J., Gudmundsson, G. H., Rottenberg, M. E., Berndt, K. D., & Agerberth, B. (1998). Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. The Journal of biological chemistry, 273(6), 3718–3724. https://doi.org/10.1074/jbc.273.6.3718
  7. Kang, J., Dietz, M. J., & Li, B. (2019). Antimicrobial peptide LL-37 is bactericidal against Staphylococcus aureus biofilms. PloS one, 14(6), e0216676. https://doi.org/10.1371/journal.pone.0216676
  8. Geitani, R., Moubareck, C. A., Costes, F., Marti, L., Dupuis, G., Sarkis, D. K., & Touqui, L. (2022). Bactericidal effects and stability of LL-37 and CAMA in the presence of human lung epithelial cells. Microbes and infection, 24(3), 104928. https://doi.org/10.1016/j.micinf.2021.104928
  9. Cirioni, O., Giacometti, A., Ghiselli, R., Bergnach, C., Orlando, F., Silvestri, C., Mocchegiani, F., Licci, A., Skerlavaj, B., Rocchi, M., Saba, V., Zanetti, M., & Scalise, G. (2006). LL-37 protects rats against lethal sepsis caused by gram-negative bacteria. Antimicrobial agents and chemotherapy, 50(5), 1672–1679. https://doi.org/10.1128/AAC.50.5.1672-1679.2006
  10. Nagaoka, I., Tamura, H., & Reich, J. (2020). Therapeutic Potential of Cathelicidin Peptide LL-37, an Antimicrobial Agent, in a Murine Sepsis Model. International journal of molecular sciences, 21(17), 5973. https://doi.org/10.3390/ijms21175973
  11. Fang, X., Nong, K., Wang, Z., Jin, Y., Gao, F., Zeng, Q., Wang, X., & Zhang, H. (2023). Human cathelicidin LL-37 exerts amelioration effects against EHEC O157:H7 infection regarding inflammation, enteric dysbacteriosis, and impairment of gut barrier function. Peptides, 159, 170903. https://doi.org/10.1016/j.peptides.2022.170903
  12. Singh, D., Qi, R., Jordan, J. L., San Mateo, L., & Kao, C. C. (2013). The human antimicrobial peptide LL-37, but not the mouse ortholog, mCRAMP, can stimulate signaling by poly(I:C) through a FPRL1-dependent pathway. The Journal of biological chemistry, 288(12), 8258–8268. https://doi.org/10.1074/jbc.M112.440883
  13. Bąbolewska, E., & Brzezińska-Błaszczyk, E. (2015). Human-derived cathelicidin LL-37 directly activates mast cells to proinflammatory mediator synthesis and migratory response. Cellular immunology, 293(2), 67–73. https://doi.org/10.1016/j.cellimm.2014.12.006
  14. Grönberg, A., Mahlapuu, M., Ståhle, M., Whately-Smith, C., & Rollman, O. (2014). Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 22(5), 613–621. https://doi.org/10.1111/wrr.12211
  15. Miranda, E., Bramono, K., Yunir, E., Reksodiputro, M. H., Suwarsa, O., Rengganis, I., Harahap, A. R., Subekti, D., Suwarto, S., Hayun, H., Bardosono, S., & Baskoro, J. C. (2023). Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial. Archives of dermatological research, 315(9), 2623–2633. https://doi.org/10.1007/s00403-023-02657-8
  16. Mahlapuu, M., Sidorowicz, A., Mikosinski, J., Krzyżanowski, M., Orleanski, J., Twardowska-Saucha, K., Nykaza, A., Dyaczynski, M., Belz-Lagoda, B., Dziwiszek, G., Kujawiak, M., Karczewski, M., Sjöberg, F., Grzela, T., Wegrzynowski, A., Thunarf, F., Björk, J., Ekblom, J., Jawien, A., & Apelqvist, J. (2021). Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 29(6), 938–950. https://doi.org/10.1111/wrr.12977
  17. Zhao, Y., Zhang, H., Zhao, Z., Liu, F., Dong, M., Chen, L., Shen, M., Luan, Z., Zhang, H., Wu, J., Li, C., Chen, J., Li, C., Liu, Z., Chen, Y., Zheng, A., Li, H., Wang, S., Jin, W., & Sun, G. (2023). Efficacy and safety of Oral LL-37 against the Omicron BA.5.1.3 variant of SARS-COV-2: A randomized trial. Journal of medical virology, 95(8), e29035. https://doi.org/10.1002/jmv.29035
  18. Sandgren, S., Wittrup, A., Cheng, F., Jönsson, M., Eklund, E., Busch, S., & Belting, M. (2004). The human antimicrobial peptide LL-37 transfers extracellular DNA plasmid to the nuclear compartment of mammalian cells via lipid rafts and proteoglycan-dependent endocytosis. The Journal of biological chemistry, 279(17), 17951–17956. https://doi.org/10.1074/jbc.M311440200
  19. Gilliet, M., & Lande, R. (2008). Antimicrobial peptides and self-DNA in autoimmune skin inflammation. Current opinion in immunology, 20(4), 401–407. https://doi.org/10.1016/j.coi.2008.06.008
  20. Yang, B., Good, D., Mosaiab, T., Liu, W., Ni, G., Kaur, J., Liu, X., Jessop, C., Yang, L., Fadhil, R., Yi, Z., & Wei, M. Q. (2020). Significance of LL-37 on Immunomodulation and Disease Outcome. BioMed research international, 2020, 8349712. https://doi.org/10.1155/2020/8349712
  21. Jiang, Y. Y., Xiao, W., Zhu, M. X., Yang, Z. H., Pan, X. J., Zhang, Y., Sun, C. C., & Xing, Y. (2012). The effect of human antibacterial peptide LL-37 in the pathogenesis of chronic obstructive pulmonary disease. Respiratory medicine, 106(12), 1680–1689. https://doi.org/10.1016/j.rmed.2012.08.018
  22. Sun, C., Zhu, M., Yang, Z., Pan, X., Zhang, Y., Wang, Q., & Xiao, W. (2014). LL-37 secreted by epithelium promotes fibroblast collagen production: a potential mechanism of small airway remodeling in chronic obstructive pulmonary disease. Laboratory investigation; a journal of technical methods and pathology, 94(9), 991–1002. https://doi.org/10.1038/labinvest.2014.86
  23. Zhang, Y., Jiang, Y., Sun, C., Wang, Q., Yang, Z., Pan, X., Zhu, M., & Xiao, W. (2014). The human cathelicidin LL-37 enhances airway mucus production in chronic obstructive pulmonary disease. Biochemical and biophysical research communications, 443(1), 103–109. https://doi.org/10.1016/j.bbrc.2013.11.074
  24. Chen, C. I., Schaller-Bals, S., Paul, K. P., Wahn, U., & Bals, R. (2004). Beta-defensins and LL-37 in bronchoalveolar lavage fluid of patients with cystic fibrosis. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 3(1), 45–50. https://doi.org/10.1016/j.jcf.2003.12.008
  25. Mahlapuu, M., Sidorowicz, A., Mikosinski, J., Krzyżanowski, M., Orleanski, J., Twardowska-Saucha, K., Nykaza, A., Dyaczynski, M., Belz-Lagoda, B., Dziwiszek, G., Kujawiak, M., Karczewski, M., Sjöberg, F., Grzela, T., Wegrzynowski, A., Thunarf, F., Björk, J., Ekblom, J., Jawien, A., & Apelqvist, J. (2021). Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 29(6), 938–950. https://doi.org/10.1111/wrr.12977
  26. Zhao, Y., Zhang, H., Zhao, Z., Liu, F., Dong, M., Chen, L., … & Sun, G. (2023). Efficacy and safety of Oral LL‐37 against the Omicron BA. 5.1. 3 variant of SARS‐COV‐2: A randomized trial. Journal of Medical Virology, 95(8), e29035.

Scientifically Fact Checked by:

Dimitar Marinov, Ph.D.

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