LL-37 dosage protocol

What LL-37 is

LL-37 is a peptide released from human cathelicidin (hCAP-18 or CAMP, hCAP18). It is a C-terminal peptide proteolytically released from the 18 kDa human cathelicidin protein (PMID 35625823, PMID 29843147, PMID 26395996). LL-37 is described as an antimicrobial peptide (AMP) and a host-defense peptide with a broad functional repertoire (PMID 38287973, PMID 26556394, PMID 36781570).

How LL-37 is thought to work

LL-37 can directly perform antimicrobial action by inserting into the surface structures of microorganisms (PMID 35625823). Its mechanisms include destruction of cell wall integrity, membrane permeabilization, induction of oxidative stress, disruption of endoplasmic reticulum homeostasis, and alterations in gene expression in fungi (PMID 38057654). For biofilms, LL-37 can inhibit bacterial adhesion, downregulate biofilm-associated genes, suppress quorum-sensing pathways, degrade biofilm matrix, and eradicate biofilm-residing cells (PMID 36781570). As an immunomodulatory molecule, LL-37 acts as an agonist of different cell membrane receptors (PMID 35625823). It can modulate inflammation, promote angiogenesis, and aid in wound healing (PMID 26556394).

What laboratory and animal studies report

LL-37 is able to inhibit the growth of clinically relevant fungi such as Aspergillus, Candida, and Trichophyton (laboratory studies, PMID 38057654). It also prevents biofilm establishment by various bacterial pathogens, including *Acinetobacter baumannii*, *Pseudomonas aeruginosa*, and *Staphylococcus aureus* (laboratory studies, PMID 36781570). In cancer, LL-37 has shown both tumorigenic effects in cancers of the ovary, lung, breast, prostate, pancreas, and malignant melanoma, as well as anti-cancer effects in colon cancer, gastric cancer, hematologic malignancy, and oral squamous cell carcinoma (laboratory studies, PMID 29843147, PMID 26395996). These effects are tissue-specific and depend on its ability to act as a ligand for different membrane receptors (laboratory studies, PMID 29843147, PMID 26395996).

Antimicrobial peptides, including LL-37, can activate the innate immune system to induce inflammation. For example, LL-37, as part of neutrophil extracellular traps (NETs), can induce Th17 in psoriatic skin (cellular studies, PMID 32947991).

Human evidence so far

Oral LL-37 expression is a factor in oral homeostasis and is involved in the development of oral dysbiosis, infections (viral, bacterial, fungal), autoimmune diseases, and oral carcinomas (human context, PMID 35625823). LL-37 has been proposed as a marker for inflammation severity and treatment outcome (human context, PMID 35625823).

In a study of Kenyan children and adolescents living with HIV (CALHIV), mean salivary cathelicidin levels were 23.7 ± 21.1 ng/mL. Children with permanent dentition and those who initiated antiretroviral therapy (ART) at or after two years old had higher mean LL-37 concentrations (human study, PMID 38287973).

Open questions and limitations

Regarding LL-37's efficacy and safety *in vivo* for antibiofilm properties, many questions remain (PMID 36781570). Further research and longitudinal studies are needed to evaluate and improve innate immunity in CALHIV (human study, PMID 38287973). The mechanisms of LL-37's contradictory effects (promoting or inhibiting tumor growth) are complex and tissue-specific (PMID 26395996).

Key terms explained

**Cathelicidin (hCAP-18/CAMP)**: The human protein from which the LL-37 peptide is derived (PMID 29843147, PMID 26395996).

**Oral homeostasis**: The stable condition of the oral cavity maintained by various factors including the oral microbiota and immune molecules (PMID 35625823).

**Oral dysbiosis**: An imbalance in the microbial community of the oral cavity (PMID 35625823).

**Biofilm**: A community of microorganisms where cells adhere to each other on a surface, often encased in an extracellular matrix (PMID 36781570).

**Immunomodulatory**: The ability to modify or regulate the immune response (PMID 35625823, PMID 36781570).