LL-37

LL-37 is a peptide your own body makes, which is unusual in this reference, where most entries cover invented molecules and a few ground up animal glands. It is the working end of the cathelicidin gene, and Gudmundsson and colleagues reported in 1996 that the human genome appears to carry only one gene of that family. Its precursor is catalogued at UniProt as P49913 and residues 134 to 170 are LL-37, thirty seven of them starting with two leucines, which is the whole of the name. That is one defined chain at a molecular weight of 4,493, so a laboratory can in principle confirm a vial holds it.

Cathelicidins are antimicrobial peptides, short protein chains that puncture bacteria, each built with a pro-region that gets cut away to release the active part. The complication, and the reason this entry spends as long on harm as on benefit, is that the same peptide has a documented role in autoimmune disease. Lande and colleagues showed in 2007 that LL-37 binds the body's own DNA and condenses it into a form taken up by the immune cells whose job is spotting viral DNA, where it trips their alarm, and in 2014 the same group found two thirds of patients with moderate to severe plaque psoriasis carrying immune cells that specifically target LL-37. A counterweight exists and deserves equal weight: mice bred without cathelicidin, given laboratory versions of lupus and arthritis, showed no difference from normal mice in autoantibodies, inflammatory signals, organ damage or arthritis severity.

Injection under the skin for infection resistance, gut health and Lyme disease. The Lyme claim is the commonest and the one to check first. Sambri and colleagues in 2002 measured five cathelicidins against the bacteria behind syphilis and Lyme disease, and for the Lyme organism the abstract reports only that all five sat between 307 and 449.4 milligrams per litre without saying which peptide sat where. Converted at a molecular weight of 4,493, that range is roughly 68 to 100 micromolar, three to eight times higher than the 13 to 25 micromolar at which this peptide damages human cells in culture.

Two things get read backwards. The first is the dose response: more is not more here, and past a point more is worse. In the first-in-man trial the highest concentration, 3.2 mg per mL, was indistinguishable from the dummy while the lowest of the three separated, and the same inversion turned up independently in a range finding study of an analogue in a completely different tissue. There is an explanation available and it is not established, so treat it as consistency rather than evidence. The second is scale. Take 500 micrograms, a molecular weight of 4,493 and a nominal three litres of plasma, ignore absorption and clearance entirely so the answer is a generous ceiling, and you get about 37 nanomolar. The concentration that stops E. coli growing is roughly 135 times higher, uninflamed tissue already carries six to thirty times more than the injection would add, and the Lyme range sits 1,800 to 2,700 times above it.

The topical record is unremarkable and worth saying so plainly. Of the 207 patients treated across the three wound trials about 135 received LL-37 rather than a dummy, and in the largest, 12 non fatal serious adverse events occurred in 11 of the 148 treated, counted across the LL-37 arms and the dummy arm together, none judged related to the drug. The injection record is three people with one published skin toxicity beside it: a 63 year old woman with stage 3C melanoma on weekly injections developed warty papules and blistering lesions after about 45 days, with eleven of twelve biopsies showing atypical squamous growth, which resolved within two months of stopping. She had been treated with nivolumab and with cisplatin, vinblastine and dacarbazine beforehand, which gives the eruption more than one candidate cause. The harder question is the autoimmune one, and it needs both halves. The record establishes that the body's own LL-37 takes part in the mechanism of psoriasis and is a target of the immune system in most patients with moderate to severe plaque disease. It does not establish that giving LL-37 to a person causes or worsens autoimmune disease, because I could not find a study that gave it to anyone with an autoimmune condition, and the injection trial I did find excluded such patients by protocol. That is an absence, not a reassurance.