Serum Levels of LL-37 and Inflammatory Cytokines in Plaque and Guttate Psoriasis

Abstract

Psoriasis is a chronic inflammatory skin disease. It is assumed that the plaque phenotype of psoriasis is associated with T helper (Th) 1 immune response activation, while the guttate phenotype is associated with the Th17 immune response. Previous investigations of differences in the serum levels of cytokines relative to the clinical psoriatic phenotype have yielded conflicting results. This study compared the levels of circulating inflammatory cytokines and LL-37 relative to the morphological phenotype in patients with psoriasis. Seventy-four age-matched patients with psoriasis (32 with guttate psoriasis and 42 with plaque psoriasis) and 12 healthy controls were included. A multiplex cytokine assay and enzyme-linked immunosorbent assay were used to measure levels of Th1- and Th17-derived cytokines and LL-37, respectively. Circulating levels of interferon- (IFN)-γ, interleukin- (IL)-1RA, IL-2, and IL-23, and LL-37 were significantly higher in patients with psoriasis than in healthy controls. However, the serum levels of inflammatory cytokines (IL-7, IL-22, and IL-23) and LL-37 did not differ significantly between the guttate and plaque phenotypes of psoriasis. There was a positive correlation between serum inflammatory cytokine levels and the Psoriasis Area and Severity Index score. The findings of this study suggest that the serum levels of inflammatory cytokines reflect the disease activity rather than determine the morphological phenotype.

The endogenous antimicrobial cathelicidin LL37 induces platelet activation and augments thrombus formation

“…11 It acts as a powerful antimicrobial peptide against bacteria, 12 fungi, 13 and viral particles 14 and modulates innate and adaptive immune responses predominantly through formyl peptide receptor 2 (FPR2/ALX). 15,16 Despite detailed research on the roles of LL37 in the modulation of inflammatory responses in various pathological settings, 17,18 its effects in the regulation of thrombosis and other platelet-related complications remained unknown for a long time. Because the level of LL37 released during inflammation is significantly higher than normal, 19,20 understanding its critical functions in the modulation of platelet reactivity will pave the way for determining fundamental mechanisms underlying platelet-related complications in various inflammatory diseases.…”

Serum level of the human antimicrobial cathelicidin (hCAP18/LL-37) in patients with psoriasis vulgaris

“…The assessed blood LL-37 in psoriasis varies substantially. The median level of LL-37 was 11.78 ng/ml (IQR 9.75 -16.90 ng/ml) in 76 studied patients with plaque and guttate psoriasis (34). Another trial assessed similar mean level of 18.16 ng/ml (range 9.1 to 35.9 ng/ml) in 100 patients with psoriasis and co-morbidities; serum LL-37 was inversely correlated with 25(OH)D (35)a lot of co-morbidities (diabetes, obesity, heart disease, etc.. Much higher concentrations of 970 ng/ml were investigated in 61 psoriatic patients by Kanda et al and the serum LL-37 did not correlate with the PASI score (36).…”

Contribution of dendritic cells to the autoimmune pathology of systemic lupus erythematosus

“…The antimicrobial peptide LL‐37, a cathelicidin polypeptide, binds self‐DNA and directs this molecule to TLR9‐containing endosomes in DCs . TLR9 ligation leads to DC activation, IFN‐ α production and possibly IC‐dependent pathogenesis during SLE and systemic autoimmune disease …”

“…69 TLR9 ligation leads to DC activation, IFN-a production and possibly IC-dependent pathogenesis during SLE and systemic autoimmune disease. [69][70][71][72] Hydroxychloroquine (HCQ), which has been demonstrated to decrease SLE flares and mortality, is able to prevent pDC activation and IFN-a production by limiting acidification and maturation of endosomes after stimulation with ligands for TLR7 and TLR9. 73,74 HCQ may inhibit TLR ligation of internalized self-DNA/RNA ICs.…”