Increased serum leucine, leucine-37 levels in psoriasis: positive and negative feedback loops of leucine, leucine-37 and pro- or anti-inflammatory cytokines

Hum Immunol. 2010 Dec;71(12):1161-71. doi: 10.1016/j.humimm.2010.09.005. Epub 2010 Sep 16.

Abstract

Expression of leucine, leucine-37 (LL-37) is enhanced in keratinocytes of skin lesions with psoriasis. We examined serum LL-37 levels in patients with psoriasis vulgaris. Serum LL-37 levels in patients were higher than in normal controls, and were reduced after cyclosporine A treatment. In both groups, LL-37 and interleukin (IL)-17 levels inversely correlated. In patients, LL-37 levels correlated with interferon (IFN)-γ and IL-10 levels. In controls, LL-37 levels inversely correlated with tumor necrosis factor (TNF)-α, IL-6, IL-1β, and IL-22 levels. IFN-γ, IL-17, IL-22, TNF-α, IL-6, and IL-1β enhanced, and IL-10, IL-4, IL-13, and cyclosporine A suppressed, LL-37 secretion from keratinocytes and neutrophils. LL-37 enhanced IFN-γ, IL-4, IL-13, and TNF-α secretion from CD3/CD28-stimulated T cells, suppressed TNF-α, IL-1β, IL-6, and IL-10 secretion from lipopolysaccharide-stimulated monocytes, and IL-17, IL-22, IL-1β, IL-6, and IL-10 secretion from CD3/CD28-stimulated T cells. LL-37 may sustain its production by enhancing IFN-γ or reducing IL-10 production, while suppressing its production by reducing IL-17, IL-22, TNF-α, IL-1β, or IL-6 and enhancing IL-4 or IL-13 production. In patients, systemic LL-37 production is enhanced, and an IFN-γ/LL-37-positive feedback loop may exist. In controls, negative feedback by LL-37 on TNF-α, IL-1β, IL-22, and IL-6 may exist. In both groups, negative feedback by LL-37 on IL-17 may exist. LL-37 may act as an effector and regulator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antimicrobial Cationic Peptides
  • Cathelicidins / blood*
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Gene Expression Regulation*
  • Humans
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Psoriasis / immunology*
  • Psoriasis / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Up-Regulation*

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Cytokines
  • Interleukin-10