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.
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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.
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.
Where to Buy LL-37 Online? | 2024 Edition
LL-37 is available for online purchase by qualified researchers and laboratory professionals.
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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.