What is LL-37?

LL-37 is an antimicrobial peptide (AMPs). It has been shown to have antimicrobial activity against multiple Gram-positive and Gram-negative human pathogens. Antimicrobial peptides (AMPs) have the potential to serve as an alternative to antibiotics. It’s simple, AMPs kill the microbial pathogens (the bugs).

AMPs can possibly regulate bacteria/virus invasion and may control infection. It has been reported that AMPs could be used to activate the innate mucosal immune response in order to get rid of the infections. (Mucosal refers to the immune response at mucosal membranes of the intestines, the urogenital tract and the respiratory system, i.e., surfaces that are in contact with the external environment).

How does LL-37 work?

LL-37 functions through several mechanisms that contribute to its role in the immune system, including direct antimicrobial activity and immunomodulatory effects. Here’s a detailed look at how LL-37 works:

• Antimicrobial Activity
  1. Membrane Disruption: LL-37 interacts with microbial cell membranes due to its amphipathic structure, which means it has both hydrophobic and hydrophilic regions. This allows LL-37 to insert itself into microbial membranes, disrupting their integrity and causing cell lysis and death.
  2. Pore Formation: LL-37 can form pores in microbial membranes, leading to the leakage of cellular contents and subsequent microbial death. This pore-forming ability is a common mechanism among antimicrobial peptides.
  3. Interaction with Microbial DNA/RNA: LL-37 can bind to microbial DNA and RNA, inhibiting essential processes such as replication and transcription, thereby preventing microbial proliferation.

• Immunomodulatory Effects
  1. Chemotaxis: LL-37 acts as a chemoattractant for various immune cells, including neutrophils, monocytes, T cells, and mast cells. By attracting these cells to the site of infection or injury, LL-37 enhances the immune response and facilitates pathogen clearance.
  2. Cytokine Modulation: LL-37 can modulate the production of cytokines, which are signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis. For instance, LL-37 can promote the production of pro-inflammatory cytokines in some contexts while inhibiting excessive inflammation in others, maintaining a balance that is crucial for effective immune responses.
  3. Wound Healing: LL-37 promotes wound healing by stimulating the migration and proliferation of epithelial cells and fibroblasts. It also enhances the formation of new blood vessels (angiogenesis) and re-epithelialization of damaged tissues.
  4. Endotoxin Neutralization: LL-37 can neutralize endotoxins such as lipopolysaccharides (LPS) from Gram-negative bacteria. By binding to LPS, LL-37 prevents it from triggering excessive inflammatory responses that can lead to sepsis.
• Additional Roles
  1. Antiviral Activity: LL-37 exhibits antiviral properties against various viruses, including HIV, influenza, and respiratory syncytial virus (RSV). It can inhibit viral entry, replication, and spread.
  2. Antifungal Activity: LL-37 is effective against fungal pathogens by disrupting fungal cell membranes and inhibiting their growth.
• Mechanisms of Regulation
  The expression and activity of LL-37 are tightly regulated at multiple levels:
  – Gene Expression: The gene encoding LL-37, CAMP, can be upregulated in response to infection, inflammation, and vitamin D signaling.
  – Post-translational Modifications: LL-37 can undergo post-translational modifications that affect its stability, activity, and interactions with other molecules.

In summary, LL-37 works through a combination of direct antimicrobial actions and complex immunomodulatory effects, making it a versatile and crucial component of the innate immune system. Its ability to disrupt microbial membranes, modulate immune cell activity, promote wound healing, and neutralize endotoxins underscores its importance in maintaining immune homeostasis and protecting the body against infections.

What you need to know:

Several studies show that LL-37 is effective in treating certain cancer cell types. LL-37 inhibits gastric cancer cell proliferation by the activation of bone morphogenetic protein (BMP) signaling. However, overexpression of LL-37 was found to promote development and progression of ovarian, lung and

Dose: 5 mg/vial

Dosing Guideline: 100-300 mcg (0.02-0.06 ml or 2-6 units) SC OD