A review of 10 antimicrobial neuropeptides — including PACAP, VIP, α-MSH, ghrelin, CGRP, substance P, and NPY — reveals their dual roles in directly fighting infections and modulating immune responses, with significant therapeutic potential for immune-related disorders.
10 neuropeptides with dual antimicrobial-immune rolesPACAP, VIP, α-MSH, ghrelin, adrenomedullin, NPY, urocortin II, CGRP, substance P, and catestatin all serve as both antimicrobial agents and immune regulators
What the researchers found
The review identifies and characterizes 10 antimicrobial neuropeptides with dual immune functions:
1. PACAP — anti-inflammatory, neuroprotective
2. VIP — immunosuppressive, anti-inflammatory
3. α-MSH — anti-inflammatory, antimicrobial
4. Ghrelin — anti-inflammatory, metabolic regulation
5. Adrenomedullin — vasodilatory, antimicrobial
6. NPY — immune cell modulation
7. Urocortin II — stress response, immunomodulation
8. CGRP — neurogenic inflammation, vasodilation
9. Substance P — pro-inflammatory, antimicrobial
10. Catestatin — antimicrobial, immune modulation
These neuropeptides share structural similarities with traditional antimicrobial peptides and are directly involved in innate immunity. Their specific receptors represent therapeutic targets for immune-related diseases.
Why it matters
The discovery that neuropeptides have antimicrobial properties blurs the traditional boundary between the nervous and immune systems. This has profound implications: it means the brain and nerves are active participants in fighting infections, not just passive bystanders. For drug development, it opens the possibility of targeting neuropeptide receptors to treat autoimmune diseases, chronic inflammation, and infections — using the body's own neuroimmune communication system as a therapeutic lever.
How the study worked
Narrative review examining the expression characteristics, antimicrobial activities, and receptor-mediated immunomodulatory mechanisms of 10 neuropeptides. The authors summarize evidence for each peptide's role in innate immunity and catalog potential drugs targeting their receptors for immune-related disorders.
What this study cannot tell us
As a narrative review, the paper synthesizes existing literature without systematic quality assessment. The antimicrobial activity of some neuropeptides has been demonstrated primarily in vitro and may not translate directly to in vivo efficacy. The therapeutic potential of targeting neuropeptide receptors for immune disorders is largely theoretical, with most drug candidates still in early development. The review covers 10 peptides broadly rather than providing deep mechanistic analysis of each.
How to read the evidence
This is a narrative review synthesizing evidence from various study types including in vitro, in vivo, and some clinical research. The evidence quality varies by peptide — some like CGRP and substance P have extensive research backing, while others like urocortin II and catestatin have more limited evidence for their antimicrobial roles.
When this study was published
Published in 2025, this is a very current review capturing the state of the art in antimicrobial neuropeptide research and neuroimmunology.
The bigger picture
The concept of neuroimmunity — the nervous system's active role in immune defense — is reshaping our understanding of both neuroscience and immunology. This review captures a key insight: many peptides we've long studied as neurotransmitters (like substance P, CGRP, NPY) are also antimicrobial agents. This dual function likely evolved because the nervous system needs to protect itself from infection, and understanding this can lead to entirely new therapeutic strategies for diseases from autoimmunity to sepsis.
Questions still open
- Which neuropeptide receptor-targeted drugs are closest to clinical application for immune disorders?
- Could combination therapies targeting multiple neuropeptide pathways simultaneously provide synergistic immune benefits?
- How do neuropeptide antimicrobial functions change with aging, potentially explaining increased infection susceptibility in older adults?
Common questions
How can a brain chemical also fight infections?
Which of these 10 neuropeptides is best known?
Read the original research
Antimicrobial Neuropeptides and Their Receptors: Immunoregulator and Therapeutic Targets for Immune Disorders.
Molecules (Basel, Switzerland), 30(3)
Citation
Chen, Kaiqi; Wu, Xiaojun; Li, Xiaoke; Pan, Haoxuan; Zhang, Wenhui; Shang, Jinxi; Di, Yinuo; Liu, Ruonan; Zheng, Zhaodi; Hou, Xitan. (2025). Antimicrobial Neuropeptides and Their Receptors: Immunoregulator and Therapeutic Targets for Immune Disorders.. Molecules (Basel, Switzerland), 30(3). https://doi.org/10.3390/molecules30030568