Study summary · research use only
Upregulating Human Cathelicidin Antimicrobial Peptide LL-37 Expression May Prevent Severe COVID-19 Inflammatory Responses and Reduce Microthrombosis
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review discusses the human cathelicidin peptide LL-37 in relation to SARS-CoV-2 infection. The abstract describes COVID-19 as involving inflammatory cytokine hyperactivation, immune cell recruitment, neutrophil extracellular trap (NET) formation, microthrombosis, and reported long-term neurological findings in humans and non-human primates. The authors describe LL-37 as an immunomodulatory host defense peptide with reported direct anti-SARS-CoV-2 activity and effects on inflammation, neovascularization, Lewy body formation, and pancreatic islet cell function, noting vitamin D and other compounds can induce LL-37 expression. The abstract hypothesizes LL-37 upregulation could support NET clearance, endothelial repair, prevention of α-synuclein aggregation, and blood-glucose stabilization, and that LL-37 may bind the SARS-CoV-2 S1 domain and mask ACE2 receptors.
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 via 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.
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