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Sander W Tas Margriet J Vervoordeldonk Najat Hajji Michael J May Sankar Ghosh Paul P Tak 《Arthritis research & therapy》2006,8(4):R86-9
Nuclear factor (NF)-κB is a key regulator of synovial inflammation. We investigated the effect of local NF-κB inhibition in
rat adjuvant arthritis (AA), using the specific IκB kinase (IKK)-β blocking NF-κB essential modulator-binding domain (NBD)
peptide. The effects of the NBD peptide on human fibroblast-like synoviocytes (FLS) and macrophages, as well as rheumatoid
arthritis (RA) whole-tissue biopsies, were also evaluated. First, we investigated the effects of the NBD peptide on RA FLS
in vitro. Subsequently, NBD peptides were administered intra-articularly into the right ankle joint of rats at the onset of disease.
The severity of arthritis was monitored over time, rats were sacrificed on day 20, and tissue specimens were collected for
routine histology and x-rays of the ankle joints. Human macrophages or RA synovial tissues were cultured ex vivo in the presence or absence of NBD peptides, and cytokine production was measured in the supernatant by enzyme-linked immunosorbent
assay. The NBD peptide blocked interleukin (IL)-1-β-induced IκBα phosphorylation and IL-6 production in RA FLS. Intra-articular
injection of the NBD peptide led to significantly reduced severity of arthritis (p < 0.0001) and reduced radiological damage (p = 0.04). This was associated with decreased synovial cellularity and reduced expression of tumor necrosis factor (TNF)-α
and IL-1-β in the synovium. Incubation of human macrophages with NBD peptides resulted in 50% inhibition of IL-1-β-induced
TNF-α production in the supernatant (p < 0.01). In addition, the NBD peptide decreased TNF-α-induced IL-6 production by human RA synovial tissue biopsies by approximately
42% (p < 0.01). Specific NF-κB blockade using a small peptide inhibitor of IKK-β has anti-inflammatory effects in AA and human RA
synovial tissue as well as in two important cell types in the pathogenesis of RA: macrophages and FLS. These results indicate
that IKK-β-targeted NF-κB blockade using the NBD peptide could offer a new approach for the local treatment of arthritis. 相似文献
3.
Johanna Westra Berber Doornbos-van der Meer Peter de Boer Miek A van Leeuwen Martin H van Rijswijk Pieter C Limburg 《Arthritis research & therapy》2004,6(4):R384
In inflammatory processes, the p38 mitogen-activated protein kinase (MAPK) signal transduction route regulates production
and expression of cytokines and other inflammatory mediators. Tumor necrosis factor α (TNF-α) is a pivotal cytokine in rheumatoid
arthritis and its production in macrophages is under control of the p38 MAPK route. Inhibition of the p38 MAPK route may inhibit
production not only of TNF-α, but also of other inflammatory mediators produced by macrophages, and indirectly of inflammatory
mediators by other cells induced by TNF-α stimulation. Here we investigate the effects of RWJ 67657, a p38 MAPK inhibitor,
on mRNA expression and protein production of TNF-α and other inflammatory mediators, in monocyte-derived macrophages. A strong
inhibition of TNF-α was seen at pharmacologically relevant concentrations of RWJ 67657, but also inhibition of mRNA expression
of IL-1β, IL-8, and cyclooxygenase-2 was shown. Furthermore, it was shown that monocyte-derived macrophages have a high constitutive
production of matrix metalloproteinase 9, which is not affected by p38 MAPK inhibition. The results presented here may have
important implications for the treatment of rheumatoid arthritis. 相似文献
4.
Yeo Dae Yoon Eun Sook Lee Jong Pil Park Mee Ree Kim Jun Won Lee Tae Hoon Kim Min Kyun Na Jin Hee Kim 《Biotechnology and Bioprocess Engineering》2011,16(6):1099-1105
Hizikia fusiforme is a commonly used food that possesses potent anti-bacterial, anti-fungal, and anti-inflammatory activities. The immunostimulatory
activities of aqueous extract of Hizikia fusiforme (HFAE) in RAW 264.7 macrophages and whole spleen cells were investigated. HFAE activated RAW 264.7 macrophages to produce
cytokines such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in
a dose-dependent manner. In addition, HFAE induced the mRNA expression of TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages.
Moreover, HFAE stimulated proliferation of whole spleen cells and reference mitogen. Taken together, the results demonstrate
that HFAE potently activates the immune function by regulating NO, TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophage and promoting
spleen cell proliferation. 相似文献
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Interleukin-17 (IL-17) is a T cell cytokine spontaneously produced by cultures of rheumatoid arthritis (RA) synovial membranes.
High levels have been detected in the synovial fluid of patients with RA. The trigger for IL-17 is not fully identified; however,
IL-23 promotes the production of IL-17 and a strong correlation between IL-15 and IL-17 levels in synovial fluid has been
observed. IL-17 is a potent inducer of various cytokines such as tumor necrosis factor (TNF)-α, IL-1, and receptor activator
of NF-κB ligand (RANKL). Additive or even synergistic effects with IL-1 and TNF-α in inducing cytokine expression and joint
damage have been shown in vitro and in vivo. This review describes the role of IL-17 in the pathogenesis of destructive arthritis with a major focus on studies in vivo in arthritis models. From these studies in vivo it can be concluded that IL-17 becomes significant when T cells are a major element of the arthritis process. Moreover, IL-17
has the capacity to induce joint destruction in an IL-1-independent manner and can bypass TNF-dependent arthritis. Anti-IL-17
cytokine therapy is of interest as an additional new anti-rheumatic strategy for RA, in particular in situations in which
elevated IL-17 might attenuate the response to anti-TNF/anti-IL-1 therapy. 相似文献
7.
Hirofumi Shoda Keishi Fujio Yumi Yamaguchi Akiko Okamoto Tetsuji Sawada Yuta Kochi Kazuhiko Yamamoto 《Arthritis research & therapy》2007,8(6):R166
IL-32 is a newly described cytokine in the human found to be an in vitro inducer of tumor necrosis factor alpha (TNFα). We examined the in vivo relationship between IL-32 and TNFα, and the pathologic role of IL-32 in the TNFα-related diseases – arthritis and colitis.
We demonstrated by quantitative PCR assay that IL-32 mRNA was expressed in the lymphoid tissues, and in stimulated peripheral
T cells, monocytes, and B cells. Activated T cells were important for IL-32 mRNA expression in monocytes and B cells. Interestingly,
TNFα reciprocally induced IL-32 mRNA expression in T cells, monocyte-derived dendritic cells, and synovial fibroblasts. Moreover,
IL-32 mRNA expression was prominent in the synovial tissues of rheumatoid arthritis patients, especially in synovial-infiltrated
lymphocytes by in situ hybridization. To examine the in vivo relationship of IL-32 and TNFα, we prepared an overexpression model mouse of human IL-32β (BM-hIL-32) by bone marrow transplantation.
Splenocytes of BM-hIL-32 mice showed increased expression and secretion of TNFα, IL-1β, and IL-6 especially in response to
lipopolysaccharide stimulation. Moreover, serum TNFα concentration showed a clear increase in BM-hIL-32 mice. Cell-sorting
analysis of splenocytes showed that the expression of TNFα was increased in resting F4/80+ macrophages, and the expression of TNFα, IL-1β and IL-6 was increased in lipopolysaccharide-stimulated F4/80+ macrophages and CD11c+ dendritic cells. In fact, BM-hIL-32 mice showed exacerbation of collagen-antibody-induced arthritis and trinitrobenzen sulfonic
acid-induced colitis. In addition, the transfer of hIL-32β-producing CD4+ T cells significantly exacerbated collagen-induced arthritis, and a TNFα blockade cancelled the exacerbating effects of hIL-32β.
We therefore conclude that IL-32 is closely associated with TNFα, and contributes to the exacerbation of TNFα-related inflammatory
arthritis and colitis. 相似文献
8.
Danielle Burger 《Arthritis research & therapy》2000,2(6):472-5
The intricate interactions that regulate relationships between endogenous tissue cells and infiltrating immune cells in the rheumatic joint, particularly in rheumatoid arthritis (RA), were the subject of the meeting. A better understanding of these interactions might help to define intervention points that could be used to develop specific therapies. The presentations and discussions highlighted the fact that, once chronic inflammation is established, several pro-inflammatory loops involving tumour necrosis factor (TNF)-α and interleukin (IL)-1β can be defined. Direct cellular contact with stimulated T lymphocytes induces TNF-α and IL-1β in monocytes which in turn induce functions in fibroblast-like synoviocytes. The latter include the production of stromal cell-derived factor-1α (SDF-1α) which enhances the expression of CD40L in T cells, which stimulates SDF-1α production in synoviocytes, which in turn protects T and B cells from apoptosis and enhances cell recruitment thus favoring inflammatory processes. IL-1β and TNF-α also induce IL-15 in fibroblast-like synoviocytes, which induces the production of IL-17 which in turn potentiates IL-1β and TNF-α production in monocyte-macrophages. This underlines the importance of TNF-α and IL-1β in RA pathogenesis, and helps explain the efficiency of agents blocking the activity of these cytokines in RA. Factors able to block the induction of cytokine production (such as apolipoprotein A-I [apo A-I] and interferon [IFN]-β) might interfere more distally in the inflammatory process. Furthermore, stimulated T lymphocytes produce osteoclast differentiation factor (ODF), which triggers erosive functions of osteoclasts. Therefore, factors capable of affecting the level of T lymphocyte activation, such as IFN-β, IL-15 antagonist, or SDF-1α antagonist, might be of interest in RA therapy. 相似文献
9.
Lee S Park HH Son HY Ha JH Lee MG Oh TY Sohn DH Jeong TC Lee SH Son JK Lee SG Jun CD Kim SH 《Cell biology and toxicology》2007,23(2):105-112
Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis.
Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin
(IL)-1β and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated
the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied
its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-α, IL-1β,
and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601
attenuated PMA- and A23187-induced activation of NF-κB as indicated by inhibition of degradation of IκBα, nuclear translocation
of NF-κB, NF-κB/DNA binding, and NF-κB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases. 相似文献
10.
Rossol M Kaltenhäuser S Scholz R Häntzschel H Hauschildt S Wagner U 《Arthritis research & therapy》2005,7(6):R1189-R1199
Stimulation of monocytes/macrophages after cell contact with preactivated T cells has been suggested to contribute to the
excessive TNF-α production in rheumatoid arthritis (RA). In this study, T cell-contact-dependent TNF-α production by peripheral-blood
monocytes in vitro was investigated and found to be significantly lower in treated and untreated patients with RA than in healthy controls.
This suppression was not due to a general deficiency of monocytes to respond, because responses to lipopolysaccharide were
comparable in patients and controls. In agreement with the pivotal role of TNF-α in RA, T cell-dependent induction of TNF-α
in synovial macrophages was fivefold to tenfold higher than in peripheral-blood monocytes from either patients or controls.
The decreased response of peripheral-blood monocytes from patients with RA was found to be mediated by inhibitory serum factors,
because the addition of patient sera to monocytes from healthy controls suppressed TNF-α response in the co-culture assay.
Preincubation of monocytes from healthy controls with RA serum was sufficient to suppress the subsequent TNF-α response in
T cell co-cultures, indicating that inhibitory factors do indeed bind to monocyte surfaces, which might represent a regulatory
counter-action of the immune system to the long-standing and consuming autoimmune process in RA. There are some indications
that apolipoprotein A-1 might be part of this regulatory system. 相似文献
11.
Bresnihan B Gogarty M Fitzgerald O Dayer JM Burger D 《Arthritis research & therapy》2004,6(6):R563-R566
The production of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) by monocytes is strongly induced by direct contact
with stimulated T lymphocytes, and this mechanism may be critical in the pathogenesis of rheumatoid arthritis (RA). Apolipoprotein
A-I (apoA-I) blocks contact-mediated activation of monocytes, causing inhibition of TNF-α and IL-1β production. This study
examined the hypothesis that apoA-I may have a regulatory role at sites of macrophage activation by T lymphocytes in inflamed
RA synovial tissue. Synovial tissue samples were obtained after arthroscopy from patients with early untreated RA or treated
RA and from normal subjects. As determined by immunohistochemistry, apoA-I was consistently present in inflamed synovial tissue
that contained infiltrating T cells and macrophages, but it was absent from noninflamed tissue samples obtained from treated
patients and from normal subjects. ApoA-I staining was abundant in the perivascular areas and extended in a halo-like pattern
to the surrounding cellular infiltrate. C-reactive protein and serum amyloid A were not detected in the same perivascular
areas of inflamed tissues. The abundant presence of apoA-I in the perivascular cellular infiltrates of inflamed RA synovial
tissue extends the observations in vitro that showed that apoA-I can modify contact-mediated macrophage production of TNF-α and IL-1β. ApoA-I was not present in synovium
from patients in apparent remission, suggesting that it has a specific role during phases of disease activity. These findings
support the suggestion that the biologic properties of apoA-I, about which knowledge is newly emerging, include anti-inflammatory
activities and therefore have important implications for the treatment of chronic inflammatory diseases. 相似文献
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Rowan S Hardy Andrew Filer Mark S Cooper Greg Parsonage Karim Raza Debbie L Hardie Elizabeth H Rabbitt Paul M Stewart Christopher D Buckley Martin Hewison 《Arthritis research & therapy》2006,8(4):R108-10
Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation.
We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of
the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Expression, activity and function of 11β-HSD1 was assessed
in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid
arthritis or osteoarthritis. 11β-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were
higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative
to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis
factor-α or IL-1β (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4-fold and 14-fold;
synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-γ was without effect, and there was no difference in 11β-HSD1
expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the
presence of 100 nmol/l cortisone, IL-6 production – a characteristic feature of synovial derived fibroblasts – was significantly
reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11β-HSD inhibitor,
emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences
in fibroblast-derived glucocorticoid production (via the enzyme 11β-HSD1) between cells from distinct anatomical locations
may play a key role in the predeliction of certain tissues to develop persistent inflammation. 相似文献
14.
Ethyl acetate extracts of alfalfa (Medicago sativa L.) sprouts inhibit lipopolysaccharide-induced inflammation in vitro and in vivo 总被引:1,自引:0,他引:1
Yong-Han Hong Wen-Wan Chao Miaw-Ling Chen Bi-Fong Lin 《Journal of biomedical science》2009,16(1):64-12
This study aimed to investigate if food components that exert anti-inflammatory effects may be used for inflammatory disorders
by examining alfalfa sprout ethyl acetate extract (ASEA). The cytokine profile and life span of BALB/c mice with acute inflammation
after intra-peritoneal (ip) injection of 15 mg/kg BW lipopolysaccharide (LPS) were determined. The results showed that the
life span of LPS-induced inflammatory mice were negatively correlated with serum levels of TNF-α, IL-6, and IL-1β at 9 hr
after LPS-injection, which indicated that suppressing these cytokines in the late phase of inflammation may be beneficial
for survival. The in vitro experiment then showed that ASEA significantly reduced IL-6 and IL-1β production and the NF-κB trans-activation activity
of mitogen-stimulated RAW264.7 cells. To further evaluate the anti-inflammatory effects of ASEA in vivo, BALB/c mice were tube-fed with 25 mg ASEA/kg BW/day in 50 μl sunflower oil, while the control and PDTC (pyrrolidine dithiocarbamate,
an anti-inflammatory agent) groups were tube-fed with 50 μl sunflower oil/day only. After one week of tube-feeding, the PDTC
group was injected with 50 mg/kg BW PDTC and one hour later, all of the mice were injected with 15 mg/kg BW LPS. The results
showed that the ASEA and PDTC groups had significantly lower serum TNF-α, IL-6, and IL-1β levels at 9 hr after LPS challenge,
and significantly higher survival rates than the control group. This study suggests that ASEA supplementation can suppress
the production of pro-inflammatory cytokines and alleviate acute inflammatory hazards. 相似文献
15.
Isidoro González-Álvaro Carmen Domínguez-Jiménez Ana M Ortiz Vanessa Núñez-González Pedro Roda-Navarro Elena Fernández-Ruiz David Sancho Francisco Sánchez-Madrid 《Arthritis research & therapy》2006,8(4):R88-11
We have characterized the lymphocyte subset and the receptor molecules involved in inducing the secretion of TNF by monocytic
cells in vitro. The TNF secreted by monocytic cells was measured when they were co-cultured with either resting or IL-15-stimulated lymphocytes,
T cells, B cells or natural killer (NK) cells isolated from the peripheral blood of healthy subjects and from the synovial
fluid from patients with inflammatory arthropathies. Co-culture with IL-15-activated peripheral blood or synovial fluid lymphocytes
induced TNF production by monocytic cells within 24 hours, an effect that was mainly mediated by NK cells. In turn, monocytic
cells induced CD69 expression and IFN-γ production in NK cells, an effect that was mediated mainly by β2 integrins and membrane-bound IL-15. Furthermore, IFN-γ increased the production of membrane-bound IL-15 in monocytic cells.
Blockade of β2 integrins and membrane-bound IL-15 inhibited TNF production, whereas TNF synthesis increased in the presence of anti-CD48
and anti-CD244 (2B4) monoclonal antibodies. All these findings suggest that the cross-talk between NK cells and monocytes
results in the sustained stimulation of TNF production. This phenomenon might be important in the pathogenesis of conditions
such as rheumatoid arthritis in which the synthesis of TNF is enhanced. 相似文献
16.
Aim The present study sought insight into the effects of remifentanyl and fentanyl on LPS-induced release of interleukin-6 (IL-6),
tumor necrosis factor-α (TNF-α) and IL-10 in human whole blood. Methods Whole blood was incubated in the presence and absence of remifentanyl and fentanyl. Effects of remifentanyl and fentanyl
on spontaneous and endotoxin (lipopolysaccharide; 100 ng ml−1)-stimulated cytokine release were studied in whole blood from volunteers (n = 10) cultured for 6 h. Results IL-6, TNF-α and IL-10 concentrations in groups added with LPS were significantly higher than those in control group (P < 0.01). IL-6, TNF-α and IL-10 concentrations in activation groups treated with remifentanyl or fentanyl were significantly
lower than those in LPS treated group (P < 0.05). There were no significant differences on IL-6,TNF-α and IL-10 concentrations in drug-alone groups compared with control
group (P > 0.05). Conclusion Remifentanyl or fentanyl alone has no effects on IL-6, TNF-α and IL-10 production, but could attenuate LPS-induced IL-6,TNF-α
and IL-10 production in human whole blood. Remifentanyl and fentanyl could inhibit the expressions of IL-6, TNF-α and IL-10
induced by LPS. 相似文献
17.
In diabetes the endothelium is either chronically or transiently exposed to hyperglycemic conditions. In addition, endothelial
dysfunction in diabetes is related to changes in the inflammatory response and the turnover of extracellular matrix. This
study was undertaken to study the effects of inflammatory stimuli on one particular matrix component, the heparan sulfate
(HS) proteoglycans (PGs) synthesized by primary human umbilical cord vein endothelial cells (HUVEC). Such cells were cultured
in vitro in 5 mM and 25 mM glucose. The latter concentration was used to mimic hyperglycemic conditions in short-term experiments.
HUVEC were also cultured in the presence of the inflammatory agents tumor necrosis factor α (TNF-α), interleukin 1α (IL-1α),
interleukin 1β (IL-1β) and transforming growth factor β (TGF-β). The cells were labeled with 35S-sulfate and 35S-PGs were recovered for further analyses. The major part of the 35S-PGs was secreted to the medium, irrespective of type of stimuli. Secreted 35S-PGs were therefore isolated and subjected to further analyses. TNF-α and IL-1α slightly increased the release of 35S-PGs to the culture medium, whereas IL-1β treatment gave a significant increase. The different treatments neither changed
the ratio of 35S-HS and 35S-chondroitin sulfate (CS) nor the macromolecular properties of the 35S-PGs. However, the 35S-HS chains were slightly increased in size after TNF-α treatment, and slightly decreased after TGF-β treatment, but not affected
by the other treatments. Compositional analysis of labeled disaccharides showed changes in the amount of 6-O-sulfated glucosamine residues after treatment with TNF-α, IL-1α and IL-1β. Western immunoblotting showed that major HSPGs
recovered from these cells were collagen XVIII, perlecan and agrin, and that secretion of these distinct PGs was increased
after IL-1β stimulation. Hence, short term inflammatory stimuli increased the release of HSPGs in HUVEC and affected both
the size and sulfation pattern of HS, depending on type of stimuli. 相似文献
18.
Berg K Chatterjee A Yasmin T Shara M Bagchi D 《Molecular and cellular biochemistry》2007,300(1-2):171-175
Helicobacter pylori, in recent years, has been recognized as the major causative agent in chronic gastritis and peptic ulcer disease in humans.
H. pylori is a ubiquitous organism, with at least half of the world’s population infected. Of those individuals with peptic ulcer disease,
it is estimated that 90% of cases are caused by H. pylori. Currently, the efficacy of therapies is starting to decline due to increasing resistance rates, especially towards clarithromycin.
Due to this, new therapies are needed to combat this bacterium. It is hypothesized that cytokine release (especially interleukin-1β,
-6, -8, and TNF-α) due to H. pylori infection and the subsequent influx of inflammatory cells causes a massive release of reactive oxygen species (ROS) during
the inflammatory reaction. The ROS then cause the pathologic changes seen in the infected tissues. In this study, human gastric
adenocarcinoma cell line ATCC 1739 (a cell line not previously evaluated) was examined for its production of interleukin-1β,
-6, -8, and TNF-α when cocultured in a ratio of 10:1 H. pylori to adenocarcinoma cells, to determine its value as a model to demonstrate the inflammatory response. Results from this study
indicated that ATCC 1739 cells only reliably produced IL-8 when cocultured with H. pylori and stimulated with TNF-α. The production of IL-1β, IL-6, and TNF-α by the ATCC 1739 cells was no different in H. pylori-exposed cells than non-exposed cells. It was concluded that the ATCC 1739 cell line is not suitable to study the effects of
coculture with H. pylori on cytokine production. 相似文献
19.
G. van Luijtelaar S. Lyashenko R. Vastyanov G. Verbeek A. Oleinik C. van Rijn G. Volokhova A. Shandra A. Coenen L. Godlevsky 《Neurophysiology》2012,43(6):478-486
We investigated the role of two cytokines, IL-1β and TNF-α, in the development of absence seizures using a genetic model of
absence epilepsy in WAG/Rij rats. We administered these cytokines to animals systemically and measured the number of spike-wave
discharges (SWDs) in the EEG. We also coadministered IL-1β with the GABA reuptake inhibitor tiagabine and measured the levels
of IL-1β and TNF-α in the brain and blood plasma of 2-, 4-, and 6-month-old WAG/Rij rats and animals that served as a non-epileptic
control (ACI). We found that IL-1β induced a significant increase in SWDs 2-5 h after administration, while TNF-α enhanced
SWDs much later. Both cytokines enhanced passive behavior; body temperature was elevated only after TNF-α. The action of tiagabine
was potentiated by earlier IL-1β injection, even when IL-1β was no longer active. Young WAG/Rij rats showed higher levels
of TNF-α in blood serum than young ACI rats; the effects in the brain tended to be opposite. The marked differences in timing
of the increase in SWDs suggest different time scales for the action of both cytokines tested. It is proposed that the results
found after TNF-α are due to the de novo synthesis of IL-1β. TNF-α may possess neuroprotective effects. IL-1β might increase GABA-ergic neurotransmission. The changes
in the efficacy of antiepileptic drugs related to changes in the cytokine systems may have some clinical relevance. 相似文献