LL–37 Side Effects
LL-37 is a tested antimicrobial peptide with great potential in eliminating various types of pathogens dangerous to the human body, such as bacteria, viruses, and fungi. The crucial function of this peptide is to regulate the inflammatory process by achieving a balance between pro-inflammatory and anti-inflammatory molecules. This property could be useful as part of the therapy for various diseases that are based on this medical process. LL-37 may also accelerate and improve the wound healing process as well as tissue recovery in general, which is important for regenerative medicine. The mechanism of action differs depending on which pathogen it is trying to eliminate. Still, it is mainly about destroying the cell wall, endangering the bacterial biofilm, or preventing further replication of the virus. It is also less known that this peptide possibly can stimulate and enhance the natural immune response and serve as an immunomodulator, which may mean a breakthrough in treating chronic infections. In addition to the above properties, this amino acid sequence also shows a potential antitumor effect, for which further research is still needed.
About the Peptide
LL-37 is a peptide from the cathelicidin AMP family, well known for its antimicrobial potential. Due to its action against most gram-positive and gram-negative bacteria, even those resistant to most medications, this peptide is called a substitute for antibiotics. This property is crucial because nowadays such infections develop very often, so therapy is often necessary. After some time, resistance of these pathogens to antibiotics occurs, and effective therapy options are required. This property does not apply only to bacteria but also to viruses and fungi. Some virions can cause serious consequences, such as influenza A or HIV, so preventing their replication is a key role of LL-37.
By regulating the course of the infection, killing or weakening the causative agent, the patient's condition is stabilized, which is the main goal of the treatment. Peptide is expressed on neutrophils in the bloodstream (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. Vitamin D (which is increased by sunlight on the skin) acts as a stimulant for neutrophils to release the peptide. Since it can regulate the inflammatory process by working on the balance between pro-inflammatory and anti-inflammatory molecules, LL-37 improves wound healing and tissue regeneration, because if it were not synthesized in sufficient quantities, the body would maintain the inflammatory state longer than necessary, which would have consequences for the body.
In medicine, this peptide could make a breakthrough in treating infections caused by Staphylococcus aureus, such as abscesses, boils, cellulitis, secondary bacterial pneumonia, or deadly infections of the blood and musculoskeletal system. This bacterium is resistant to most antibiotics, and studies indicate that short-term treatment with this peptide led to a significant reduction in the number of biofilm colonies. In addition, scientists are studying the effect of this peptide on certain cancer cells. It is believed that it is possible to inhibit growth and prevent further cell proliferation. However, as it is also possible to worsen the condition of other organs such as the ovaries, lungs, or breasts, so additional research is needed to reduce the possibility of this negative effect, because in this case it may cause or worsen an already existing malignancy.
All of the above properties make LL-37 a peptide of great importance for potential therapy in cases of various diseases. In contrast, immunomodulation and potentiation of the natural immune response make this peptide even more useful.
How This Peptide Works
The mechanism of action and how LL-37 works differ depending on the indication for use. It represents one of the first lines of defense of the body against pathogens, so if the type of microorganism being fought is bacteria, the defense is most often reflected in binding to the cell wall and its destruction, as well as acting on cytoplasmic structures, or interrupting the possibility of creating dangerous bacterial endotoxins. There are also types of such microorganisms that are resistant to antibiotics because they produce different types of enzymes. By disrupting their biofilm, this peptide can potentially be effective, even against them.
Regarding viruses, LL-37 works not only by binding to the cell but also by interrupting their further replication. These pathogens enter human cells and begin to multiply to cause damage, so by acting on their nucleic acid (RNA or DNA) that they need in that process, the peptide directly destroys the virus. Before that, it can work on the disintegration of the virus envelope, and later on the elimination of this virus with the help of antibodies.
LL-37 fights fungi similarly, by increasing the permeability of the fungal cell membrane and disrupting its balance and interfering with its further function in the human body. Immunomodulatory activity and the ability of the peptide to enhance the natural immune response (most often from the mucous membrane) are crucial for treating urogenital, intestinal, and respiratory infections, because these are parts of the body that come into contact with the external environment. This amino acid sequence could effectively treat staphylococcal bacteria, especially Staphylococcus aureus, which can cause serious, even fatal infections. LL-37 has shown potential to kill not only cell-bound bacteria, but also those that are completely free in the bloodstream. Given that this pathogen does not respond to most conventional antibiotics, this could be a serious advance in treating acute and chronic types of this infection. In this case, the mechanism of action is mainly reflected in the destruction of biofilms. The main property of this peptide is precisely the regulation of inflammation, which comes as a defense of the body against the presence of pathogens. However, if it persists for a long time, inflammation can have consequences for the body. This peptide maintains a balance between molecules that potentiate and those that prevent inflammation. Therefore, wounds can heal without interference, tissue recovers faster and more efficiently.
Structure of LL-37
The three-dimensional structure of LL-37 consists of a long helix containing four exons, the fourth of which encodes the antimicrobial domain for which this peptide is known. The entire chemical structure consists of three-hundred-and-eight atoms.
Side Effects
The Appearance of Rosacea
Rosacea is a chronic skin condition whose etiology is not fully understood. Scientists assume that high levels of LL-37 peptide are responsible for the symptoms of redness, swelling, and visible veins. Studies have confirmed this assumption because after deliberate injection of this peptide, rosacea appeared in experimental animals. A high degree of aggregation of inflammatory cells, thickening of the epidermis and dermis, and deposition of collagen were found. If patients take LL-37 for any indication, they further increase the levels of this natural peptide, thereby increasing the chance of this unwanted effect occurring. This undesirable effect requires mandatory treatment by a dermatologist.
Other Skin Reactions
In addition to clinical rosacea, other skin reactions such as telangiectasia (widened veins, most often localized on the face), papules, or unusual erythema may occur as side effects of this peptide. The above-mentioned phenomena can also be symptoms of rosacea if they occur together, but very often they occur completely unrelated. All of the above effects should be treated by a doctor.
Occurrence and Progression of Malignancy
Because of its ability to activate bone macrophage protein (BMP) signaling, which can inhibit the growth of certain cancer cells (such as stomach tumors) and prevent them from spreading to other organs, LL-37 is considered a potential part of the therapy of some cancers. However, the main reason why this benefit is taken with caution is that it comes with serious side effects. It is possible that this type of signaling can cause or worsen malignancies in certain organs, such as the primary ovaries, but also the breast or lung.
Injection Site Reactions
There are several ways to administer this peptide, subcutaneous administration is considered the safest and most common. There is always a chance of mild and short-term but common side effects. These include redness, swelling, or skin reaction at the application site. Check such phenomena, especially if the skin reaction persists, because one of the serious side effects of this peptide is rosacea. There is often a clear difference, but it is always recommended to consult with a doctor.
Safety
Serious side effects that could be dangerous to the patient and require medical treatment almost always occur only as a result of excessive dosage and irresponsible consumption. If LL-37 is taken as indicated, under the supervision of a doctor, and at the recommended dosage, it is a completely safe substance to consume with many beneficial effects. This peptide will certainly be the subject of research in the future.