LL-37 vs Vasoactive Intestinal Peptide (VIP)
A neutral, side-by-side comparison of two healing & recovery peptides — their mechanisms, dosing ranges, administration routes, side effects, and research evidence. For research and educational purposes only.
LL-37
LL-37 is the only human cathelicidin — a host defense peptide produced by neutrophils, epithelial cells, and macrophages in response to infection and inflammation. It functions simultaneously as a broad-spectrum antimicrobial agent and an immune-modulatory signaling molecule. Research interest has expanded dramatically since COVID-19 studies linked low LL-37 levels to severe outcomes, and gut health research identified it as a key regulator of intestinal barrier integrity.
Full profileVasoactive Intestinal Peptide (VIP)
28-amino acid neuropeptide found throughout the CNS, gut, and immune system. Functions as a potent anti-inflammatory, vasodilator, and neurotrophic factor. Research applications include CIRS (Chronic Inflammatory Response Syndrome), pulmonary arterial hypertension, autoimmune conditions, and gut motility disorders. Intranasal administration is most studied for CIRS and neuroinflammatory conditions.
Full profile| LL-37 | Vasoactive Intestinal Peptide (VIP) | |
|---|---|---|
| Category | Healing & Recovery | Healing & Recovery |
| Also known as | Cathelicidin LL-37, hCAP-18 C-terminal fragment, CRAMP (murine equivalent) | VIP, vasoactive intestinal polypeptide, PHM-27 |
| Evidence | Research-stage | Investigational (in trials) |
| Dosing range | 100mcg–500mcg mcg, Daily or 3–5x weekly | 25mcg–100mcg mcg, Daily intranasal or 1–2x weekly subcutaneous |
| Administration | Subcutaneous injection, Intranasal (for respiratory applications), Topical (wound care) | Intranasal spray, Subcutaneous injection, Inhalation (nebulized) |
| Key side effects | Injection site redness and irritation (common — pro-inflammatory at injection site), Transient flu-like symptoms (immune activation), Local induration, High doses may be cytotoxic — dose-response curve is non-linear | Facial flushing, Transient hypotension, Nasal irritation (intranasal route), Tachycardia |
| Cited sources | 3 references | 2 references |
Key differences
- Evidence level differs: LL-37 is research-stage, while Vasoactive Intestinal Peptide (VIP) is investigational (in trials).
- Administration: LL-37 — Subcutaneous injection, Intranasal (for respiratory applications), Topical (wound care); Vasoactive Intestinal Peptide (VIP) — Intranasal spray, Subcutaneous injection, Inhalation (nebulized).
- Frequency: LL-37 is typically Daily or 3–5x weekly; Vasoactive Intestinal Peptide (VIP) is Daily intranasal or 1–2x weekly subcutaneous.
- Research depth: this profile cites 3 sources for LL-37 vs 2 for Vasoactive Intestinal Peptide (VIP).
How each works
LL-37
LL-37 exerts antimicrobial activity by disrupting bacterial membranes via electrostatic interaction with negatively charged lipopolysaccharide — effective against gram-positive and gram-negative bacteria, fungi, and enveloped viruses including SARS-CoV-2 in vitro. Beyond direct antimicrobial action, LL-37 modulates innate immunity through TLR4 signaling, promotes wound healing via EGFR and FPRL1 receptor activation, and has demonstrated anti-biofilm activity against P. aeruginosa and S. aureus. Vitamin D is the primary driver of endogenous LL-37 production.
Vasoactive Intestinal Peptide (VIP)
VIP activates VPAC1 and VPAC2 receptors coupled to cAMP, suppressing pro-inflammatory cytokines while promoting Th2 regulatory immune responses and Treg differentiation. In the CIRS/biotoxin illness framework pioneered by Shoemaker, VIP intranasal formulation demonstrates normalization of inflammatory markers and improvement in TGF-β, MSH, and VIP deficiency seen in CIRS patients. Pulmonary vasodilation effects have been studied for PAH.
This comparison aggregates public research and structured profile data for informational purposes only. It is not medical advice and does not recommend either compound for human use. Consult a qualified healthcare provider before considering any peptide.