Peptide Primer: LL-37, Super Antibiotic You Make on Your Own

August 05, 2019

ReferencesWikipediaScience DirectCritical CareFront ImmunolFuture Microbiol., ScienceCell PhysJr Biomed SciDermatoendocrinology,

Did you know you make an antibiotic called Cathelicidin? Yup! It's a peptide otherwise known as LL-37. It makes a circular pore that basically binds to the cell wall of bacteria and then makes all their guts leak out. You don't make it until your Vitamin D level is 32. Now, in Wisconsin, our D levels get to around 20 in the winter if you are Caucasian and less if you have any pigment in your skin. In summer, Wisconsin Caucasians get to 45 and make Vitamin D in response to sunlight. More skin pigment, less Vitamin D production (but better folate protection). Consequence: we get more flu and colds in winter because of less Vitamin D, resulting in lower cathelicidin. We used to treat tuberculosis by sending folks off to the mountains where they got fresh mountain air and sat in the sun. (So, they were actually getting more UVB radiation at high altitude, making more Vitamin D - raising their cathelicidin levels: LL-37) 

Ok, so you tell me what you think would happen with patients in an ICU with sepsis, systemic infection in their blood when you study Vitamin D and cathelicidin levels. You got it. In 121 ICU patients, those with the top third of Vitamin D levels had 4.5 times LESS mortality than those in the bottom third, which also correlated with their LL-37 levels. Know any antibiotic that works that well? Hmmm. How about looking at over 10,000 patients starting dialysis and examining mortality from infection over the next year. Again, the lowest third of Vitamin D and LL-37 have double the mortality from infection. 

Let's expand our view of our immune system and look at cancer. What role does LL-37 play here? Once again, we find that Vitamin D turns on cathelicidin/LL-37 and that kills cancer cells. The mechanism in cancer doesn't appear to be quite as simple as in bacteria where LL-37 just punctures a hole in the wall. In cancer, LL-37 binds to the surface of the cancer cell and mucks up its reproduction. But it works, on almost every kind of cancer.

Any human studies with LL-37 given in sepsis? Not that I can find. Lot's of mice and rat studies, where it shows it helps. But we are getting a little far off the reservation when we jump to humans.

The theory is good. The toxicity is low. The activity is there. Would you do it?

WWW: What will work for me. This is the dilemma we are in. We can now purchase these powerful chemicals on the gray market. Not super cheap but not unattainable. The ability to manufacture them allows a new frontier of medical exploration. Am I ready for using it? Not really sure until you get into the right circumstance. If all else is failing, would you add this to your armamentarium? What I would do is make dead certain my Vitamin D level is sufficient. We are now nearing fall when the angle of the sun becomes such that we don't make enough Vitamin D. 100,000 a month, 20,000 a week, 5,000 a day are doses that work. Do one of them.

Pop Quiz

  1. LL-37 is what?                      Answer: a peptide we mammals make that kills bacteria and viruses.
  2. How does it do it?               Answer: It burrows into the cell wall of the bacteria and all their contents leak out.
  3. What Vitamin induces you to make your own LL-37?                 Answer: Vitamin D
  4. What blood level  of Vitamin D do you need to have to make your own LL-37/cathelicidin?             Answer: 32
  5. Do we get more cancer in winter than in summer? (Just like more flu). Answer: Yup!