Cathelicidins, Defensins and their Important Interactions with Leukotriene B4

 Studies suggest that human cathelicidins (LL-37) and Leukotriene B4 may work in a positive feedback loop, meaning they may both stimulate each other for enhanced immunei response:

• Leukotriene B4 triggers release of the cathelicidin LL-37 from human neutrophils: novel lipid-peptide interactions in innate immune responses
• Leukotriene b4 triggers the in vitro and in vivo release of potent antimicrobial agents
• Leukotriene B4/antimicrobial peptide LL-37 proinflammatory circuits are mediated by BLT1 and FPR2/ALX and are counterregulated by lipoxin A4 and resolvin E1

And several studies suggest that Leukotriene B4, cathelicidins and defensins indeed play a very important role together in controlling infections:

• LTB4 increases nasal neutrophil activity and conditions neutrophils to exert antiviral effects
• Intrapulmonary administration of leukotriene B4 enhances pulmonary host defense against pneumococcal pneumonia
• Leukotriene B(4)-Mediated Release of Antimicrobial Peptides against Cytomegalovirus Is BLT1 Dependent
• Leukotrienes play a role in the control of parasite burden in murine strongyloidiasis.
• Inhibition of leukotriene biosynthesis abrogates the host control of Mycobacterium tuberculosis.
• Leukotriene B4 protects latently infected mice against murine cytomegalovirus reactivation following allogeneic transplantation.
• Leukotriene-deficient mice manifest enhanced lethality from Klebsiella pneumonia in association with decreased alveolar macrophage phagocytic and bactericidal activities
• Release of anti-HIV mediators after administration of leukotriene B4 to humans.
• Leukotriene B(4) induces nitric oxide synthesis in Trypanosoma cruzi-infected murine macrophages and mediates resistance to infection.
• Possible role of LTB4 in the antiviral activity of turbot (Scophthalmus maximus) leukocyte-derived supernatants against viral hemorrhagic septicemia virus (VHSV).
• Role of mast cell leukotrienes in neutrophil recruitment and bacterial clearance in infectious peritonitis.
• Leukotriene B4 Induces Release of Antimicrobial Peptides in Lungs of Virally Infected Mice
• Leukotriene B4-loaded microspheres as a new approach to enhance antimicrobial responses in Histoplasma capsulatum-infected mice

 Many herbal supplements and prescription and non-prescription drugs are known to block production of Leukotriene B4 either by inhibiting all downstream leukotriene products of the 5-Lipoxygenase (5-LOX) pathway or by blocking Leukotriene B4 (LTB4) directly.   Below is a list of several herbal supplement or prescription and non-prescription drugs that studies suggest may inhibit the 5-LOX pathway or block LTB4 directly: 

Prescription and Non-Prescription Drugs:

• Itraconazole (LTB4)
• Licofelone
• Montelukast (Singulair) - cys-LT / LTB4 antagonist
• Oxymetazoline
  • Drugs.com: Oxymetazoline nasal
  • Drugs.com: Oxymetazoline opthalmic
• Zileuton (Zyflow)
• Celebrex

 Herbal Sources:

• Boswellia
• Caffeic Acid (White grapes, white wine, olives, olive oil, spinach, cabbage, asparagus, and coffee)
• Curcumin / Turmeric
• Eugenol (Cloves)
• Ginger
• Hyperforin (St John's Wort)
• Milk Thistle / Silymarin / Silibinin
• Quercetin
• Green Tea Catechin
• Lyprinol
• Resveratrol
• Arnica montana
• Chamomile
• Hamamelis virginian
• Hypericum perforatum (St John's Wort)
• Echinacea angustifolia