What Is KPV?

KPV is a tripeptide consisting of three amino acids: Lysine-Proline-Valine. It represents the C-terminal sequence (positions 11-13) of alpha-melanocyte stimulating hormone (α-MSH), a hormone with well-documented anti-inflammatory properties.

Sequence: Lys-Pro-Val (KPV) Molecular Weight: 342.43 g/mol Origin: C-terminal of α-MSH (positions 11-13) Category: Anti-inflammatory peptide

What makes KPV unique is that it retains the anti-inflammatory properties of α-MSH without affecting melanocortin receptor signaling — meaning it doesn't cause skin tanning or other melanocortin-related effects.

Key Characteristics

  • Size: Smallest fragment of α-MSH with anti-inflammatory activity
  • Receptor Independent: Works without melanocortin receptor binding
  • Research Focus: Inflammatory bowel disease, skin inflammation
  • Advantage: No pigmentation effects unlike α-MSH

Mechanism of Action

KPV exerts anti-inflammatory effects through several distinct pathways:

NF-κB Inhibition

A primary mechanism involves inhibition of nuclear factor kappa-B (NF-κB):

  • Prevents translocation of NF-κB to the nucleus
  • Reduces transcription of pro-inflammatory genes
  • Decreases production of cytokines like TNF-α, IL-1β, and IL-6

Direct Cellular Entry

Unlike α-MSH, KPV can enter cells directly:

  • Penetrates cell membranes without receptor binding
  • Acts intracellularly on inflammatory pathways
  • Can reach the nucleus to modulate gene expression

Inflammasome Modulation

Research suggests KPV may affect inflammasome activity:

  • Potential NLRP3 inflammasome inhibition
  • Reduced IL-1β and IL-18 processing
  • Dampened pyroptotic cell death

Research Areas

Inflammatory Bowel Disease (IBD)

The most extensive research involves gastrointestinal inflammation:

  • Colitis Models: Reduced inflammation severity in multiple animal studies
  • Mucosal Healing: Promoted intestinal epithelial repair
  • Cytokine Reduction: Decreased inflammatory mediators in gut tissue
  • Oral Delivery: Unique ability to retain activity when given orally (in some studies)

Skin Inflammation

Dermatological research has explored several applications:

  • Contact dermatitis models
  • Allergic skin reactions
  • Wound healing with reduced inflammation
  • Psoriasis models

Antimicrobial Properties

Emerging research indicates potential antimicrobial effects:

  • Activity against certain bacteria (Staphylococcus aureus)
  • Antifungal properties in some studies
  • Potential synergy with antibiotics

Other Research Areas

  • Arthritis: Joint inflammation models
  • Lung inflammation: Acute lung injury studies
  • Ocular inflammation: Eye inflammation models
  • Central nervous system: Neuroinflammation research

Key Published Studies

Year Focus Area Key Finding Reference
2003 Mechanism NF-κB pathway inhibition identified Ichiyama et al.
2008 Colitis Reduced inflammation in IBD model Kannengiesser et al.
2013 Gut healing Enhanced intestinal wound repair Xiao et al.
2017 Oral delivery Demonstrated oral bioactivity Dalmasso et al.
2020 Antimicrobial Antibacterial activity confirmed Singh & Bhalla

Comparison with α-MSH

KPV vs α-MSH

  • Size: KPV is 3 amino acids; α-MSH is 13 amino acids
  • Pigmentation: KPV — none; α-MSH — causes tanning
  • Receptor Binding: KPV — independent; α-MSH — MC receptors
  • Anti-inflammatory: Both retain this activity
  • Stability: KPV may be more stable due to smaller size

Research Administration Routes

KPV has been studied via multiple administration routes:

  • Oral: Unique among peptides — some studies show retained activity
  • Topical: Skin inflammation applications
  • Subcutaneous: Systemic inflammation studies
  • Rectal: Direct colon delivery for colitis research

Research Status

KPV remains a research peptide and has not been approved for human therapeutic use. While preclinical research is promising, particularly for inflammatory conditions, human clinical trials are needed to establish safety and efficacy. Current use is limited to laboratory research.

Summary

KPV represents an elegant example of how a small peptide fragment can retain significant biological activity. Its receptor-independent mechanism, lack of pigmentation effects, and potential for oral activity make it a unique subject in anti-inflammatory peptide research. The growing body of evidence in IBD and skin inflammation models continues to drive scientific interest in this tripeptide.

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