LL-37

Overall Health Benefits of LL-37

• Significantly boosts immune function [1-19]
• Fights inflammation [20-29]
• Prevents cancer progression [30-59]
• Accelerates wound healing [60-67]
• Lowers the risk of heart disease [68-70]
• Prevents lung injury [71-72]
• Promotes bone repair [73-77]

What is LL-37?

LL-37, also known as Human Cathelicidin Antimicrobial Peptide (CAMP), is touted as a “mammal’s core tool” to fight off various harmful microorganisms in the body. It’s produced by many cell types including natural killer (NK) cells, white blood cells, and skin cells. In addition, different body systems such as the respiratory system, gastrointestinal tract, testes, and ocular surface also produce LL-37. This powerful peptide has piqued the interest of the research community because its immune-modulating activities have the potential to accelerate tissue recovery and significantly improve the survival rate of patients with chronic debilitating medical conditions.

How LL-37 Works?

The human cathelicidin LL-37 serves a critical role in the innate immune system by defending against bacterial infections. LL-37 can interact with the molecules of the cell wall and perforate cytoplasmic membranes resulting in bacterial cell death. In addition, LL-37 helps promote wound closure by stimulating the formation of new blood vessels (angiogenesis).

Chemical Structure of LL-37

Research on LL-37

Significantly Boosts Immune Function

An overwhelming body of research shows that this antimicrobial peptide regulates various important mechanisms involved in immune function:

1. LL-37 boosts immune function by limiting the damage caused by bacterial products and recruiting immune cells to the site of infection. [1]
2. A cell study found that LL-37 has the ability to inhibit the formation of bacterial biofilms (densely packed communities of microbial cells). [2]
3. A cell study also found that LL-37 may help enhance the immunomodulatory function of human placenta-derived MSCs (pMSCs). [3]
4. A study found that LL-37 was deadly against Staphylococcus aureus, the most common cause of upper respiratory tract infections. [4]
5. LL-37 demonstrated strong antimicrobial activity against eye pathogens (infectious microorganisms). [5]
6. Studies showed that LL-37 destroyed harmful microorganisms by inducing programmed cell death (apoptosis). [6-8]
7. A study found that LL-37 can kill a broad spectrum of bacteria. [9-10]
8. LL-37 boosts immune response by attracting immune cells including T cells, monocytes, neutrophils, and mast cells to the site of infection. [11-12]
9. LL-37 also affects the maturation of dendritic cells (antigen-presenting cells). [13]
10. LL-37 stimulates the production of immune cells such as cytokines, chemokines, and their receptors. [14-15]
11. Higher blood levels of LL-37 were associated with a lower risk of death from infection in dialysis patients. [16]
12. In patients with psoriasis, LL-37 worked synergistically with human beta-defensin 2 (HBD-2) in killing Staphylococcus aureus (S. aureus) bacteria. [17]
13. A study showed that LL-37 may be beneficial in treating patients with sepsis. [18]
14. A study showed that LL-37 enhanced the effects of lysozyme against S. aureus. [19]

Fights Inflammation

Aside from its immune-boosting properties, LL-37 also has potent anti-inflammatory activity according to high-quality studies:

1. In patients who had surgical removal of the tonsils, those with high levels of LL-37 had lesser inflammation compared to those with low LL-37. [20]
2. LL-37 suppresses the translocation of NF-kB to the nucleus, which creates an anti-inflammatory effect. [21]
3. In mice, LL-37 administration reduced the risk of inflammatory disease. [22]
4. LL-37 reduces inflammation by modulating inflammatory pathways in the body. [23-25]
5. In human gum cells, LL-37 strongly reduced the levels of pro-inflammatory cytokines and chemokines. [26]
6. LL-37 also modulates the inflammatory and host defense response of human white blood cells. [27]
7. In mouse models, LL-37 provided protection against collagen damage which normally occurs in inflammatory arthritis. [28]
8. A study showed that LL-37 was effective in regulating inflammation induced by interleukin-32. [29]

Prevents Cancer Progression

Studies show that LL-37 can help ward off deadly cancers:

1. A cell study found that LL-37 has the potential to suppress cancer growth. [30]
2. In another cell study, LL-37 suppressed the growth of colon cancer by inducing programmed cell death. [31]
3. A study found that LL-37 has an anti-cancer effect in colon cancer, gastric cancer, skin cancer, ovarian cancer, lung cancer, breast cancer, prostate cancer, hematologic malignancy, and oral cancer. [32]
4. In various human cancer cell lines, LL-37 exhibited anti-cancer effects similar to chemotherapeutic drugs. [33]
5. In human lung cancer cell lines, LL-37 suppressed cancer progression by reducing the production of pro-inflammatory cytokines. [34]
6. Cell studies have shown that LL-37 can inhibit the migration and invasiveness of prostate cancer cells. [35-40]
7. In colon cancer, gastric cancer, and skin cancer cell lines, treatment with LL-37 prevented cancer cell progression.[41-46]
8. In colon cancer cell lines, LL-37 destroyed cancer cells by stimulating signaling pathways involved in programmed cell death. [47-51]
9. In gastric cancer cell lines, LL-37 inhibited gastric cancer cell proliferation through activation of signaling pathways involved in cell cycle arrest. [52-55]
10. In leukemic cell lines, recombinant LL-37 treatment killed malignant cells by activating programmed cell death. [56-57]
11. In human oral cancer cell lines, treatment with LL-37 destroyed malignant cells by damaging their DNA. [58-59]

Accelerates Wound Healing

Studies also show that this peptide can help stimulate faster regeneration of wounds:

1. In patients with venous leg ulcers, LL-37 treatment was associated with a faster healing rate (almost six-fold higher) compared to placebo. [60]
2. In mice, LL-37 treatment promoted wound healing through the production of new blood vessels. [61]
3. A cell study found that LL-37 induces wound healing by stimulating the proliferation and migration of cells necessary for regeneration. [62]
4. In mice, LL-37 treatment improved re-epithelialization and granulation tissue formation – both of these processes are necessary for wound healing. [63-64]
5. Cell studies found that LL-37 improves wound healing through its antimicrobial activity. [65-66]
6. In patients with venous leg ulcers, low-dose LL-37 treatment markedly decreased the mean ulcer area. [67]

Lowers the Risk of Heart Disease

LL-37 has also been found to possess cardioprotective effects:

1. A study showed that LL-37 can protect against atherosclerosis (plaque build-up within the heart arteries). [68]
2. A study also found that LL-37 inhibited cell death in the heart, suggesting that increasing its level might have therapeutic benefits against heart failure. [69]
3. In mice, heart failure was associated with a decrease in LL-37 levels and this deficiency worsened the condition. [70]

Prevents Lung Injury

Studies found that LL-37 is essential for healthy lungs:

1. In mice, LL-37 attenuated the progression of lung injury by controlling inflammation and preventing infection. [71]
2. A study reported that LL-37 is an effective inflammatory regulator in various lung diseases. [72]

Promotes Bone Repair

Evidence also suggests that LL-37 is vital for bone repair:

1. A mice study found that LL-37-treated white blood cells promoted bone formation. [73]
2. Cell studies also found that LL-37 can help prevent bone disorders by inhibiting bone breakdown. [74-75]
3. In rats with bone defects, LL-37 treatment markedly induced newly formed bones. [76]
4. A cell study reported that LL-37 induced bone formation by recruiting stem cells into the site of injury. [77]

Associated Side Effects of LL-37

LL-37 side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on LL-37. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of LL-37. Despite this, it was listed as a side effect associated with LL-37 even though these associated side effects are very uncommon.

Side effects associated with LL-37 may include the following:

• Increased inflammation
• Induction of autoimmune disease
• Depression
• Damage to sperm surface membranes

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