Session Information
Date: Tuesday, November 10, 2015
Title: Spondylarthropathies and Psoriatic Arthritis Pathogenesis, Etiology Poster I
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Axial spondyloarthritis
(axSpA) defines a group of chronic inflammatory diseases which includes non-radiographic
axSpA (nr-axSpA) who do not have definite sacroiliitis on pelvic X-rays. Disease
burden seems to be similar between nr-axSpA and AS, however differences or similarities
in disease progress and pathogenesis are not completely clear. Thymoquinone (TQ) is
the active ingredient of Nigella sativa and it’s anti-inflammatory,
anticancer and immunoregulatory role has been demonstrated
in various diseases. The aim of this study was to investigate the cytokine production
of peripheral blood mononuclear cells (PBMC) in pts with axSpA (AS and
nr-axSpA) and the effect of thymoquinone on the
cytokine profile.
Methods: Pts with axSpA
who met the ASAS axSpA classification criteria and age-matched healthy controls
(HC) were enrolled in this study. Pts were DMARD naive (biologic or synthetic),
and 23 pts were using only NSAIDs (19 on demand, 5 regular full dose). All of
the pts had pure axial involvement and none had peripheral arthritis or
psoriasis or IBD. Peripheral blood mononuclear cells (PBMCs) were cultured in
RPMI medium with and without TQ (12.5 µM ). PBMCs were
stimulated for 48 hours with 10 µg/ml phytohemagglutinin
and secretion of TNF-α, interleukin-4 (IL4), IL6, IL8, IL10, IL17 and VEGF was measured in the
supernatant by ELISA (lab investigators were blind to pts/controls clinical
diagnosis/variables).
Results: Twenty-nine pts
with axSpA (14 male, 37.2±12.6 yrs) and age- and gender-matched 14 healthy
controls (7 male, 35.6±9.6 yrs) were included. In axSpA group 15 pts were
nr-axSpA (mean symptom duration; 5.3±6.7 yrs) and 14 pts were AS (10.4±8.6 yrs).
Disease activity assessed by BASDAI and ASDAS-CRP were similar in pts with AS
(4.4±2.3 and 2.9±1.3) and nr-axSpA (3.8±1.9 and 2.6±1.1). Cytokine levels
without TQ are given in Table 1. Interleukin-4 (Il-4), Il-8, TNF-α and VEGF were significantly different in pts with axSpA
compared to HCs. Cytokine profiles were similar in pts with AS and nr-axSpA. TQ supressed cytokine secretion in pts
with axSpA and HCs (Table 2). However VEGF secretion increased with TQ,
particularly in pts with AS (nr-axSpA 18.4±5.1 vs AS 29.1±13.2 pg/ml, p=0.011).
Conclusion: This is the first study reporting similar cytokine profile of stimulated
PBMCs in patients with AS and nr-axSpA and the suppressive effect of TQ on
cytokine production of PBMCs. Also our results showed increased production of VEGF
by PBMCs despite TQ particularly in patients with AS.
Acknowledgement: This
study is supported with a grant from Scientific Research Projects Unit of our
university TTU-2013-4890.
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Table 1. Cytokine levels between axial spondyloarthritis and healthy controls (HCs) (pg/ml, mean±SEM)
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|||||||
|
|
HCs (n=14)
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axSpA (n=29)
|
P
|
AS(n=14)
|
p
|
nr-axSpA (n=15)
|
p
|
|
IL-4
|
226.7 ± 12.8 |
203.5 ± 18. 2 |
0.022 |
216.2 ± 33.3 |
0.250 |
191.7 ± 17.3 |
0.060 |
|
IL-6
|
1906.8 ± 305.8 |
2806.1 ± 420.3 |
0.328 |
3667.5 ± 688.5 |
0.054 |
2002.2 ± 420.6 |
0.694 |
|
IL-8
|
13095.2± 2063.9 |
26257 ± 859.1 |
˂0.0001 |
26908.2 ± 719.0 |
˂0.0001 |
25649.3 ± 1533.3 |
˂0.0001
|
|
IL-10
|
1091.2 ± 233.2 |
1641.8 ± 52.2 |
0.106 |
1686.4 ± 306.7 |
0.108 |
1600.2 ± 275.3 |
0.163 |
|
IL-17
|
432.5 ± 84.8 |
350.1 ± 40.7 |
0.857 |
319.6 ± 50.6 |
0.383 |
378.6 ± 63.8 |
0.777 |
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TNF-α
|
739.9 ± 77.4 |
0.009
|
506.4 ± 56.55 |
0.029
|
645.0 ± 84.3 |
0.432 |
|
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VEGF
|
6.9 ± 3.1 |
20.6 ± 4.6 |
0.001
|
27.0 ± 8.7 |
0.001
|
14.6 ± 3.5 |
0.007
|
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Table 2. Comparisons of cytokine levels with and without thymoquinone in HCs and axSpA (pg/ml, mean±SEM)
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pg/ml mean±SEM
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HCs+TQ (n=14)
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HCs vs HCs+TQ p
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axSpA+TQ(n=29)
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axSpA vs axSpA+TQ p
|
|
IL-4
|
159.5 ± 7.5 |
0.002
|
190.7 ± 8.6 |
0.754
|
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IL-6
|
31.8 ± 2.9 |
0.001
|
24.7 ± 4.5 |
0.002
|
|
IL-8
|
357.4 ± 19.9 |
0.001
|
679.4 ± 273.8 |
0.002
|
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IL-10
|
5.2 ± 1.7 |
0.001
|
3.3 ± 0.8 |
0.002
|
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IL-17
|
9.6 ± 4.3 |
0.001
|
7.1 ± 2.4 |
0.002
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TNF -α
|
246.6 ± 12.3 |
0.001
|
270.1 ± 17.54 |
0.002
|
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VEGF
|
18.0 ± 4.5 |
0.002
|
23.6 ± 2.1 |
0.859 |
To cite this abstract in AMA style:
Kilic E, Sakalar C, Aksu H, Cakir M, Kilic G, Ozgocmen S. Cytokine Secretion By Peripheral Blood Mononuclear Cells in Patients with Axial Spondyloarthritis and the Effect of Thymoquinone on Cytokine Profile [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/cytokine-secretion-by-peripheral-blood-mononuclear-cells-in-patients-with-axial-spondyloarthritis-and-the-effect-of-thymoquinone-on-cytokine-profile/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/cytokine-secretion-by-peripheral-blood-mononuclear-cells-in-patients-with-axial-spondyloarthritis-and-the-effect-of-thymoquinone-on-cytokine-profile/