Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of collagen-induced arthritis.
Chow. Leola N Y LN; Choi. Ka-Yee Grace KY; Piyadasa. Hadeesha H; Bossert. Maike M; Uzonna. Jude J; Klonisch. Thomas T; Mookherjee. Neeloffer N
Key Findings
- IG‑19 peptide reduced arthritis severity in a mouse model
- IG‑19 lowered antibodies against collagen type II and cut joint inflammation and cartilage loss
- A different cathelicidin‑derived peptide (IDR‑1018) did not show these benefits
Practical Outcomes
- For now the result is mainly scientific proof‑of‑concept that a human‑derived peptide can dampen autoimmune joint inflammation without hurting infection defenses. Biohackers should treat it as an interesting lead to watch, but there’s no safe dosage or protocol for human use yet.
Summary
A small piece of the human immune protein LL‑37, called IG‑19, was given to mice with a rheumatoid‑arthritis‑like disease and it lowered joint damage, inflammation and disease‑related antibodies. The same effect wasn’t seen with a similar peptide from cows. The work is still in animals, so it’s not a ready‑to‑use treatment for people yet.
Abstract
Current therapies for autoimmune chronic inflammatory diseases e.g. rheumatoid arthritis (RA) include inhibitors of inflammatory cytokines. However, these therapies can result in increased risk of infections. There is a need to explore alternate strategies that can control inflammation without compromising the innate ability to resolve infections. In this study, we examined the effect of small peptides derived from endogenous cathelicidin peptides in a murine model of collagen-induced arthritis (CIA). Cathelicidins are immunomodulatory peptides known to control infections. We demonstrate that the administration of the peptide IG-19, which represents an internal segment of the human cathelicidin LL-37, decreased disease severity and significantly reduced the serum levels of antibodies against collagen type II in the CIA model. IG-19 peptide reduced cellular infiltration in joints, prevented cartilage degradation and suppressed pro-inflammatory cytokines in the CIA mice. We also showed that not all cathelicidin-derived peptides exhibit similar functions. A bovine cathelicidin-derived peptide IDR-1018 did not exhibit the beneficial effects observed with the human cathelicidin LL-37-derived peptide IG-19, in the same murine model of CIA. This is the first study to provide evidence demonstrating the ability of a peptide derived from the human cathelicidin LL-37 to alleviate the arthritic disease process in a murine model of RA. Our results has lead us to propose a new approach for controlling autoimmune chronic inflammatory disorders such as RA, by using specific synthetic derivatives of endogenous host defence peptides. Cathelicidin-derived peptides are particularly attractive for their dual antimicrobial and anti-inflammatory actions.
Study Information
pubmed
2013
2013-10-01T00:00:00.000Z
10.1016/j.molimm.2013.08.011
42
56