LL–37 Dosage
LL-37 is a well-known antimicrobial peptide. The study's results indicate its great potential in the fight against various types of pathogens that attack the human body, including bacteria, viruses, and fungi. This property applies primarily to a wide range of gram-positive and gram-negative bacteria, which is also known as an alternative to antibiotics. The mechanism of action differs depending on the pathogen it acts on. In the case of bacterial strains, it most often destroys the bacterial membrane or disrupts the biofilm in antibiotic-resistant bacteria.
The effect on viruses is mainly reflected in disrupting their further replication. LL-37 could control infection in the ways above, which is an ideal basis for treating various diseases that have this process as their basis. Lesser known but equally useful, effects of this peptide are reflected in the potentiation and activation of the innate immune response (most often from the mucosa), but also in the treatment of chronic persistent infections. There are studies on the anti-tumor effect of LL-37, but further research is necessary.
Dosage Chart
Timeline |
Week 1 – 4 |
Week 5 – 6 |
Week 7 – 10 |
Dosing of LL-37 for immunomodulatory activity protocol |
125mcg (one subcutaneous injection per day) |
Pause |
125mcg (one subcutaneous injection per day) |
About the Peptide
LL-37 is a peptide with high antimicrobial potential. It can potentially be used in various bacterial, fungal, and viral infections, where it regulates their course, kills the causative agent, and stabilizes the patient's condition. LL-37 belongs to the AMP cathelicidin family. It is expressed in circulating neutrophils (a type of white blood cell), bone marrow cells, cells in the walls of the stomach and intestines, as well as in the epididymis and lungs. Neutrophils need stimulation, most often in the form of vitamin D (which is released in increased amounts under the influence of sunlight on the skin), to release the peptide. LL-37 is one of the members of the first line of defense against the microbiome and can be effective in accelerating the wound healing process.
The mechanism of action differs depending on the type of pathogen that affects the body. Suppose it is a bacterium (various types of gram-positive and gram-negative strains). In this case, the peptide works to destroy the bacterial membrane by binding to the cell wall and destroying cytoplasmic structures but also disrupts the balance of the biofilm of bacteria that are resistant to antibiotics (which happens in some strains as a result of enzyme production). Another way to fight these microorganisms is to inactivate the process of creating bacterial endotoxins. The effect on viral pathogens is reflected in preventing their further replication. Viruses are divided into RNA and DNA types according to their hereditary material. To cause damage to our body, these microorganisms plow into our cells and start replicating. Therefore, LL-37 not only inhibits binding to our cells but also works on the crucial part, which is multiplication. It does this by disintegrating the virus envelope, acting on the nucleic acid, and later it can also work on removing the virus with the help of antibodies. When fighting fungi, LL-37 exerts its effect by disrupting the integrity of the membrane and making it permeable. This disrupts the balance in the cell and reduces the stability of the fungal structure. It can also affect the composition of the cell wall, thereby interfering with its function.
All of the above properties, as well as the way it fights pathogens in the form of immunomodulation make this peptide very potent in treating various diseases. It also accelerates the natural immune response from the mucosa, which is important in the case of urogenital, respiratory, and digestive tract infections. This peptide is given special importance because the previous therapy, especially against bacterial infections, in the form of antibiotics, has become problematic due to the creation of resistance. Nowadays, such inflammations are common, so long-term antibiotic therapy becomes a problem.
List of Uses for This Peptide
LL-37 as Part of the Therapy of Staphylococcal Infections
The staphylococcal group is best known for its main representative, Staphylococcus aureus (the great staphylococcus). This bacterium is not always serious but can cause skin and soft tissue infections such as abscesses, furuncles, and cellulitis. Deadly bloodstream infections, bacterial secondary pneumonia, and bone and joint infections can also be caused by this pathogen, and the biggest problem is resistance to most antibiotics, so active work is being done on adequate therapy against Staphylococcus aureus. According to many studies, LL-37 has proven to be effective in the fight against this microorganism. Not only has it shown the ability to destroy bacteria when they invade cells, but it has also shown the same effect when they are completely free in the bloodstream. This potential can also be useful in the fight against chronic infections that do not respond to classical therapy, since it has shown better results than most conventional antibiotics available. Scientists assume that they will be able to use this function in immunocompromised patients, such as diabetics, HIV-positive patients, or people without a spleen, who often develop infections because their immune defense is very weak. The mechanism of action is associated with the destruction of the biofilm of this bacterium. After many tests, the results showed a significantly lower number of colonies than after treatment with the antibiotics used so far. With the destroyed biofilm, the bacteria weaken and their resistance to therapy decreases.
LL-37 in the Process of Wound Healing and Tissue Repair
When a pathogen of any kind invades the body, macrophages that are closest to the entry point take over the microorganism in an attempt to destroy it. They do this by releasing large amounts of free oxygen radicals that destroy the pathogen in the process of phagocytosis. Macrophages send signals to the body that it needs to set up a line of defense, and the body responds by releasing pro-inflammatory cytokines and creating inflammation. The inflammatory reaction is normal and represents a way to fight against the pathogen. However, it can also lead to inadequate wound healing, create scars, and, if not controlled, this reaction of the body can lead to autoimmune diseases. The main role of LL-37 is precisely to maintain the balance between pro-inflammatory and anti-inflammatory molecules, so that the body is vital enough to defend itself with the help of its own mechanisms, but also to be able to preserve its own health. With the help of this peptide, tissue heals faster, wounds recover completely because it acts on macrophages to send signals to stop inflammation at the right time, when the body has recovered sufficiently, and there is no need for further reactions that would damage health.
LL-37 in Cancer Treatment
Although the topic of cancer therapy has been studied for years and is broad, LL-37 has shown some potential in treating certain cancer cells. This does not refer to the general pattern of cancer formation, but to the suppression of further growth of precisely defined cells. Certain studies show that the peptide can activate bone macrophage protein (BMP) signaling, which can further inhibit the proliferation of cancer cells. This mechanism could potentially be part of the therapy for gastric cancer. However, overexpression of LL-37 could worsen the condition of other organs and lead to the development or progression of already existing malignancies in the ovaries, lungs, and breasts.
Dosage Calculator
During the study of the adequate dose, as well as different administration methods, the optimal dosage values have changed. Today, studies indicate a dose of 125 mcg, which is used as a subcutaneous injection once a day for the first 4 weeks.
After that, taking a break of at least two weeks is necessary to avoid potential side effects. In the period from 7 to 10 weeks, the peptide is applied in the same way and amount as in the first therapy window. This protocol is followed regarding indications in the form of various infections, where the peptide serves as an antimicrobial and anti-inflammatory compound. LL-37 must be used according to indications, under the supervision of a doctor, and in the exact dosage.
Conclusion
LL-37 is a peptide from the AMP cathelicidin family, and has a high antimicrobial activity. Scientists assume it could be very effective as part of the therapy against viral, fungal, or bacterial infections. Some of the most prominent effects relate to treating Staphylococcus aureus and more efficient wound healing and tissue repair. There are also assumptions that this peptide could be effective in the fight against certain cancer cells, but this property is still being studied. This peptide will certainly be the subject of research in the future.