This study assessed IL-17 production in patients with psoriasis and the role of histamine and histamine H3/H4 receptors. IL-17 production was higher in psoriasis patients compared to healthy donors, as measured by ELISA of PBMC culture supernatants. Histamine increased IL-17 production in psoriasis patient PBMC by up to 60%, an effect diminished by the H3/H4 antagonist ciproxifan. This modulatory effect of histamine was more pronounced in psoriasis patients with high BMI compared to normal BMI. The results suggest IL-17 production in psoriasis is regulated by histamine and H3/H4 receptors, especially

1. #212 - Thematic Poster Session (TPS)
(212) Histamine and H3/H4 Histamine Receptors are Involved in IL-17 Synthesis in Patients
with Psoriasis
Khanferyan R.1, Gevorkyan L.1, Dubuske L. M.2,3
1 Peoples' Friendship University of Russia, Moscow, Russia
2 mmunology Research Institute of New England, Gardner, United States
3 George Washington University School of Medicine, Washington, United States
CONCLUSIONS
RESULTS
METHODS
ABSTRACT
INTRODUCTION
Psoriasis is a chronic, immune-mediated, inflammatory disease that is pathogenically driven
by proinflammatory cytokines. Psoriasis is a chronic, systemic, hyper-proliferative immune-
mediated inflammatory skin disease. The results of epidemiological investigations have
shown that psoriasis affects around 2% of the general population worldwide. It is common
skin disease with a high negative impact on patients' quality of life and mediated several
pro-inflammatory cell types, such as T-cells, antigen-presenting cells e.c. which disturbed
keratinocyte differentiation. There are several clinical forms of psoriasis, including plaque
psoriasis, psoriasis guttate, psoriasis arthropathia, pustular psoriasis, psoriasis erythroderma,
and inverse psoriasis. The most common type of psoriasis is psoriasis vulgaris, which
accounts for 85–90% of all cases, an immune-mediated inflammatory skin disease with
involvement of pro-inflammatory cytokines may be impacted by white adipose tissue which
activates the inflammation by production of adipokines and cytokines. It has been known
since the last two decades that psoriasis has a greater tendency to associate with obesity and
its other metabolic syndromes. Many cytokines are involved in psoriasis development. Our
previous studies demonstrated the impact of several pro-inflammatory cytokines (IL-6, IL-8,
IFNγ, IL-17, IL-18 and TNFa) on the development of psoriasis and the concentrations them
highly increased in psoriasis patients with increased body mass index. However, last
investigations identify IL-17A as the major effector cytokine driving pathogenesis. After
recent discovery of the novel Th17 cell type producing IL-17 and IL-22 it was realized that
both T cell types (Th1 and Th17), are present in the psoriatic lesion, and Th17 cells have
great importance in the development of psoriasis. Moreover it have been shown that In
psoriasis, IL-23 is overproduced mainly by dendritic cells and stimulates survival and
proliferation of Th17 cells. A critical function of Th17 cells in psoriasis rather than of Th1
cells had been accepted and led to reclassify psoriasis as a more Th17-driven disease. Th17
cells are implicated in the pathogenesis of psoriasis by producing high amounts of IL-17A
and IL-22 (Boutet et al., 2018). Accordingly, biologics (like, Brodalumab) that target IL-17A
function lead to rapid and dramatic improvement of skin and joint symptoms in psoriasis.
Taking in account that histamine levels are also highly elevated in inflamed skin, it is likely
that histamine plays a relevant role in psoriasis pathology. Most of previous studies with
antagonists of histamine H1 receptor or H2 receptors, nevertheless were clinically ineffective
in reducing chronic symptoms in psoriasis. Over the last years, the new types of histamine
(H3 and H4) receptors with approximate 50% of similarities have demonstrated. The previous
researches shown that H4 type antagoinists display anti-inflammatory effects in mouse model
as well as in clinical trials and therefore might present a novel therapeutic target. This study
assesses the serum levels of pro-inflammatory cytokines and adipokines in patients with
psoriasis of varied body mass index (BMI).
59 patients with psoriasis with varied skin lesions and severity aged
from 18 to 50 years old were assessed. In vitro synthesis of IL-17 was
assayed in PBMC culture of patients with psoriasis of various localization of
lesions and disease severity as well as various body mass index (BMI) . The
concentrations of IL-17A in supernatants of 48h-cultivated PBMC from
There was a greater than 2 fold increase in production of IL-17 in in
sera of patients with psoriasis compared to healthy donors (fig.1)
(p<0.05).
PBMC from psoriasis patients cultivated in the presence of
histamine highly increase up to 60% production of IL-17 (fig. 2)
The in vitro effects was diminished in cell cultures pre-cultivated with
Ciproxifan (table 1) and effects were more pronounced in patients with
high BMI (26-30) compared to patients with normal BMI (21-25).
1. IL-17A serum production and synthesis in vitro by
mononuclear cells in psoriasis patients is higher than in
healthy donors
2. IL-17A production in psoriasis patients is modulated by
histamine and histamine H3/H4 receptors, with greatest
effects seen psoriasis patients with high BMI.
0
10
20
30
40
50
60
Control BMI 20-25 BMI 26-30
IL-17
pg/ml
Fig. 1 The concentration of IL-17 in sera of psoriasis patients
with different BMI
Table 1
The influence of H3/4 histamine antagonist on the IL-17 synthesis by PBMC of psoriasis
patients with different body mass index
BMI 21-25 BMI 26-30
Control 4,86 8,65
PBMC + Ciproxifan 10-5M
3,60*
(p<0/05)
5,28**
(p<001)
RATIONALE: Psoriasis is an immune-mediated inflammatory skin disease wherein
Th17 cells producing IL-17 are present driving psoriasis pathogenesis. Synthesis of
IL-17 by peripheral blood mononuclear cell (PBMC) of patients with psoriasis and the
role of histamine and H3/H4 histamine receptors in the regulation of IL-17 production
was assessed in this study.
METHODS: In vitro synthesis of IL-17 was assayed in PBMC culture of patients with
psoriasis of various localization of lesions and disease severity as well as various body
mass index (BMI) . The concentrations of IL-17 in supernatants of 48h-cultivated
PBMC from psoriasis patients and healthy volunteers were examined by ELISA. To
assess the impact of histamine, PBMC were cultivated in the presence of histamine
and the histamine H3/H4antagonist Ciproxifan.
RESULTS: There was a greater than 2 fold increase in production of IL-17 in patients
with psoriasis compared to healthy donors (p<0.05). PBMC from psoriasis patients
cultivated in the presence of histamine highly increase up to 60% production of IL-17;
this effect was diminished in cell cultures pre-cultivated with Ciproxifan. These effects
were more pronounced in patients with high BMI (26-30) compared to patients with
normal BMI (21-25).
CONCLUSIONS: IL-17 production in psoriasis patients is modulated by histamine
and histamine H3/H4 receptors, with greatest effects seen psoriasis patients with high
BMI.