What Is LL-37?

LL-37 is the only known human cathelicidin, which is a large protein family with diverse function. These peptides, which are primarily found in macrophages and polymorphonuclear leukocytes (both types of white blood cell), are important for killing bacteria, but have been found to have other dramatic effects as well. The entire class is often referred to as antimicrobial peptides (AMPs). LL-37 has been found to play important roles in autoimmune disease, cancer, and wound healing.

LL-37, while primarily billed as an antimicrobial peptide, actually plays a role in a number of inflammatory diseases such as psoriasis, lupus, rheumatoid arthritis, and atherosclerosis. Depending on the local inflammatory environment and the particular cells involved, LL-37 has several different immune system modulating behaviors.

Interestingly, LL-37 does not affect the immune system in the same way all of the time. Research in cell culture has shown that the inflammatory environment affects how cells of the immune system respond to LL-37. T-cells, for instance, will increase their inflammatory actions in response to LL-37 when they are not activated but decrease inflammatory action when already activated.

It appears that LL-37 has potent homeostatic effects, helping to balance the immune response and prevent it from becoming overactive in the setting of infection. These findings would suggest that LL-37 could play a role in helping to regulate the unchecked inflammation of autoimmune diseases. This may explain why there has been a strong correlation between LL-37 levels and autoimmune disease. It was previously thought that LL-37 might be causing autoimmune inflammation, but more recent evidence suggests that high levels of LL-37 in autoimmune disease may actually be preventing more fulminant inflammation.