Upregulating Human Cathelicidin Antimicrobial Peptide LL-37 Expression May Prevent Severe COVID-19 Inflammatory Responses and Reduce Microthrombosis.
Aloul. Karim M KM; Nielsen. Josefine Eilsø JE; Defensor. Erwin B EB; Lin. Jennifer S JS; Fortkort. John A JA; Shamloo. Mehrdad M; Cirillo. Jeffrey D JD; Gombart. Adrian F AF; Barron. Annelise E AE
Key Findings
- LL‑37 can directly inhibit SARS‑CoV‑2 and modulate inflammation
- Higher LL‑37 levels may improve clearance of neutrophil traps and reduce micro‑thrombosis
- Vitamin D and several other agents are known to increase LL‑37 expression
Practical Outcomes
- For biohackers, a practical step is to ensure adequate vitamin D status (e.g., 2000–5000 IU/day, depending on blood levels) as a safe way to potentially raise LL‑37. Adding other LL‑37 inducers (like certain short‑chain fatty acids or curcumin) may further boost the peptide, but users should treat these suggestions as experimental and monitor health markers closely.
Summary
The paper proposes that boosting the natural peptide LL‑37—using vitamin D and other safe compounds—might help calm the over‑active immune response seen in severe COVID‑19, clear harmful clots, protect blood vessels, support insulin release, and even guard against brain changes linked to Parkinson‑like symptoms. However, the ideas are based on existing knowledge and hypotheses, not on new human trials.
Abstract
COVID-19 is characterized by hyperactivation by inflammatory cytokines and recruitment of macrophages, neutrophils, and other immune cells, all hallmarks of a strong inflammatory response that can lead to severe complications and multi-organ damage. Mortality in COVID-19 patients is associated with a high prevalence of neutrophil extracellular trap (NET) formation and microthrombosis that are exacerbated by hyperglycemia, diabetes, and old age. SARS-CoV-2 infection in humans and non-human primates have revealed long-term neurological consequences of COVID-19, possibly concomitant with the formation of Lewy bodies in the brain and invasion of the nervous system <i>via</i> the olfactory bulb. In this paper, we review the relevance of the human cathelicidin LL-37 in SARS-CoV-2 infections. LL-37 is an immunomodulatory, host defense peptide with direct anti-SARS-CoV-2 activity, and pleiotropic effects on the inflammatory response, neovascularization, Lewy body formation, and pancreatic islet cell function. The bioactive form of vitamin D and a number of other compounds induce LL-37 expression and one might predict its upregulation, could reduce the prevalence of severe COVID-19. We hypothesize upregulation of LL-37 will act therapeutically, facilitating efficient NET clearance by macrophages, speeding endothelial repair after inflammatory tissue damage, preventing α-synuclein aggregation, and supporting blood-glucose level stabilization by facilitating insulin release and islet β-cell neogenesis. In addition, it has been postulated that LL-37 can directly bind the S1 domain of SARS-CoV-2, mask angiotensin converting enzyme 2 (ACE2) receptors, and limit SARS-CoV-2 infection. Purposeful upregulation of LL-37 could also serve as a preventative and therapeutic strategy for SARS-CoV-2 infections.
Study Information
pubmed
2022
2022-05-12T00:00:00.000Z
10.3389/fimmu.2022.880961
37
195