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LL-37: A New Era in Regeneration and Immunotherapy

Modern medicine is intensively searching for new strategies to overcome the limits of traditional therapies. At the forefront of interest is LL-37, the only known human cathelicidin, which has captivated the scientific community with its complex biological effects.

LL-37 stands out for its unique set of properties. It acts as an uncompromising “destroyer” of pathogens, but also sensitively regulates the immune response, dampens chronic inflammation and stimulates the repair of damaged tissues. Its multifunctional effect goes beyond conventional therapeutics, which is a unique advantage in a time of increasing antibiotic resistance.

In the clinical and dermatological context, it opens the door to innovative approaches for the treatment of chronic wounds, inflammatory skin deposits or regeneration of damaged tissues, without the need for aggressive interventions, with respect for the physiological balance of the organism.

More than just an antimicrobial peptide

Antibiotic resistance claims hundreds of thousands of premature deaths each year and deprives health systems of billions of dollars. According to the World Health Organization, it is one of the greatest global threats of our time. Interventions that were routine not so long ago are now teetering on the edge of safety because of the ineffectiveness of available antibiotics.

The emergence and spread of multidrug-resistant bacterial strains, the so-called “superbugs”, is occurring faster than the development of new therapeutics. Drugs that were considered effective in the past are now failing, and common infections are turning into life-threatening diseases. The development of new types of antimicrobial agents has never been more urgent.

LL-37 appears to be a promising candidate to address this problem. It attacks directly on the cell membranes of pathogens, leading to their immediate destruction. This property is particularly valuable in the fight against resistant bacteria. At the same time, it does not exert a selection pressure favouring the emergence of resistance, which fundamentally distinguishes it from conventional antimicrobials.

However, LL-37 does not only affect pathogens, but also the immune response itself. It can activate or suppress inflammatory processes depending on the body’s needs. In the case of infection, it increases the production of pro-inflammatory cytokines, but it can also dampen inflammatory responses in chronic or autoimmune diseases, thereby protecting tissues from excessive damage.

Potential of LL-37 in the treatment of cancer

LL-37 promotes wound healing by stimulating angiogenesis and keratinocyte migration. In a randomised, double-blind, placebo-controlled clinical trial, researchers investigated the efficacy of a cream containing LL-37 peptide in the treatment of diabetic ulcers with mild degrees of infection. Patients applied either LL-37 cream or placebo twice a week for four weeks.

During the entire follow-up period (days 7, 14, 21, and 28), the LL-37 group achieved significantly higher values of the granulation index – a parameter reflecting new tissue formation. Statistical significance was demonstrated at all measured time points, indicating that LL-37 effectively accelerates tissue regenerative processes. Other studies have demonstrated its potential in the treatment of psoriasis.

In the field of oncology, LL-37 is being investigated for its ability to retard the growth of tumour cells. Preclinical studies show that LL-37 can inhibit tumour cell proliferation through multiple mechanisms, including apoptosis, cell cycle disruption, or modulation of the immune response.

The most pronounced anti-tumour effects have been observed in malignant melanoma. In pancreatic cancer, LL-37 restricts the ability of cells to migrate and penetrate into the environment. In colorectal carcinoma, it actively slows the proliferation of cancer cells while blocking the signalling pathways responsible for the spread of metastases. In gastric cancer, it slows tumour growth, and in some forms of leukaemia, it significantly boosts the immune system.

LL-37 brings a ‘fresh wind’ to the development of therapeutic and dermo-cosmetic solutions. Its endogenous origin, combined with its high biological affinity and versatility to act in a variety of environments, predispose this peptide for incorporation into novel, breakthrough therapeutic approaches.

 

 

SOURCES:

https://pmc.ncbi.nlm.nih.gov/articles/PMC7565865/

https://pmc.ncbi.nlm.nih.gov/articles/PMC8227053/

https://pmc.ncbi.nlm.nih.gov/articles/PMC10514151/

https://pmc.ncbi.nlm.nih.gov/articles/PMC9445486/

 

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