Blood Serum Levels of IL-2, IL-6, IL-8, TNF-α and IL-1β in Patients on Maintenance Hemodialysis

Cytokines are essential mediators of immune response and inflammatory reactions. Patients with chronic renal failure (CRF) commonly present with abnormalities of immune function related with impaired kidney function and the accumulation of uremic toxins in addition to bioincompatibility of dialyzer membranes. During a hemodialysis (HD) session, cytokines are released mainly by monocytes activated by endotoxin-type compounds in dialyzer fluid, complement factors and direct contact with dialyzer membrane. The study included 15 CRF patients, aged 36.4±2.9 years, on regular HD maintenance therapy for mean 68±10 months and 15 healthy controls. It was designed to assess serum levels of a panel of inflammatory cytokines: IL-1β, IL-2, IL-6, IL-8 and TNF-αin CRF patients on regular maintenance HD before, 20, 60 and 240 minutes of a single HD session in parallel with C-reactive protein (CRP) as an additional parameter. CRP concentration was increased in HD patients when compared with healthy controls. The concentrations of IL-1, IL-6, IL-8 and TNF-αwere increased, whereas the serum level of IL-2 was not altered during a single HD session.     

Polymorphisms in the Genes Encoding TGF-��1, TNF-��, and IL-6 Show Association with Type 1 Diabetes Mellitus in the Slovak Population

Numerous cytokines have been shown to participate in the pathogenesis of type 1 diabetes (T1D). As gene polymorphisms can influence cytokine production or function, they may potentially contribute to genetic predisposition to the disease. The aim of this study was therefore to investigate the role of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine and cytokine receptor genes in genetic susceptibility to T1D. Polymerase chain reaction with sequence-specific primers was used to genotype cytokine SNPs and HLA-DRB1 alleles in 151 diabetics and 140 healthy individuals of Slovak origin. Univariate analysis showed that transforming growth factor (TGF)-β1 codon 10 TT homozygotes were significantly more susceptible to developing T1D than C allele carriers (P _c = 0.0066, OR = 2.46). Furthermore, tumor necrosis factor (TNF)-α −308 A allele carriers were also significantly overrepresented among the diabetics (P _c = 0.0031, OR = 2.62); however, the association of the −308 A allele with T1D might be due to its strong linkage disequilibrium with the susceptibility allele HLA-DRB1*0301. An association was also found with interleukin (IL)-6 −174 G/C and nt565 G/A SNPs; however, its significance was lost when statistical correction was applied. These data suggest that the TGF-β1 codon 10 SNP is among numerous genetic variations with small individual effects on T1D development. Moreover, a possible role of TNF-α and IL-6 SNPs cannot be ruled out, although their association with T1D was due to strong LD with the HLA class II susceptibility allele or did not withstand statistical correction, respectively.     

Study on the relationship of hypotestosteronemia and IL-1,TNFα in infertility rabbits with vasovasotomy

Study on the relationship of hypotestosteronemia and IL-1,TNFα in infertility rabbits with vasovasotomy     

Involvement of glutamate NMDA and AMPA receptors, glial cells and IL-1β in the spinal hyperalgesia evoked by the chemokine CCL2 in mice

We study here the involvement of excitatory amino acid receptors, glial cell activation and IL-1β release in the spinal hyperalgesia evoked by the chemokine CCL2 (MCP-1). Three hours after the intrathecal administration of CCL2 (1-100 ng), mice exhibit dose-dependent thermal hyperalgesia, that was inhibited by the coadministration of the antagonist of chemokine receptor type 2 (CCR2) RS504393 (0.3-3 μg). To assess the involvement of excitatory amino acid receptor sensitisation, CCL2 was coadministered with CPP (0.3-3 ng) and NBQX (25-250 ng), antagonists of NMDA and AMPA receptors, respectively. Both drugs blocked CCL2-evoked hyperalgesia, strongly suggesting that CCL2 evokes in vivo NMDA and AMPA receptor sensitisation, as previously described in electrophysiological studies. Furthermore, this rapid induction of CCL2-mediated hyperalgesia was blocked by the previous acute administration of the microglial inhibitor minocyclin (4.9 μg) or the astroglial inhibitor l-aminoadipate (1.6 μg). Since IL-1β can be released by activated glial cells we tested whether this cytokine could be underlying the spinal sensitisation induced by CCL2. The administration of the type I IL-1 receptor antagonist, IL-1ra (3-30 μg), partially prevented CCL2-evoked hyperalgesia. Finally, to elucidate if IL-1β could produce NMDA and AMPA receptor sensitisation by itself, we performed experiments in which this cytokine was i.t. administered. Thermal hyperalgesia induced by IL-1β (30 pg) was completely prevented by the coadministration of CPP (3 ng) but unaffected by NBQX (250 ng). Globally, our results suggest that spinal CCL2 induces thermal hyperalgesia by sensitising NMDA and AMPA receptors in a process that involves glial activation and IL-1β release.     

BamH1 polymorphism in the Chinese,Malays, and Indians in Singapore and its application in the prenatal diagnosis of β-thalassemia

Summary The distribution of restriction fragment length polymorphism (RFLP) at theBamH1 site of the -globin gene was investigated in the Chinese, Indian, and Malay race in Singapore. The sample comprised of 183 normal individuals and 35 -thalassemia carriers in which 13 were couples with at least one -major child. The results from this study indicate thatBamH1 polymorphism will be informative in 22% of pregnancies at risk for -thalassemia major in Chinese, 19% in Malays and 7% in Indians. In prenatal diagnosis usingBamH1 polymorphism for one -major affected family, the fetus was diagnosed to be normal or -carrier. The validity ofBamH1 polymorphism in the exclusion of -thalassemia major was subsequently confirmed at birth by globin chain biosynthesis.     

Influence of LPS, TNF, TGF-ß1 and IL-4 on the expression of MMPs, TIMPs and selected cytokines in rat synovial membranes incubated in vitro

Synovial membranes are formed by four main types of cells, i.e. fibroblasts, macrophages, epitheliocytes and adipocytes. To study the combined effect of various factors on these cell populations, synovial membranes dissected from rat knee joints were incubated in control medium or medium with lipopolysaccharide (LPS), TNF, TGF-?1 or IL-4 for 12 h. LPS stimulated TNF secretion and both agents stimulated secretion of IL-6. TGF-?1 slightly increased IL-6 secretion. LPS increased the mRNA levels of IL-6, IL-1?, TGF-?1, MMP1a, MMP1b, MMP3, MMP9, MMP13, MMP14, TIMP1 and TIMP3 while the mRNA levels of MMP2, TIMP2 and TIMP4 were significantly decreased. Expression of IL-1?, MMP1a, MMP1b, MMP3, MMP9, MMP13 and TIMP1 increased after TNF treatment, while mRNA levels of MMP2, MMP14, TIMP2, TIMP3 and TIMP4 were decreased. TGF-?1 decreased the mRNA levels of IL-1?, all MMPs, TIMP1, TIMP2, TIMP4 and increased mRNA levels of itself and TIMP3. IL-4 decreased mRNA levels of IL-1?, TGF-?1, MMP2, MMP9, MMP13 and all TIMPs. Only LPS decreased the amount and activity of MMP2. The effect of LPS and cytokines on most of the MMPs and TIMPs produced by whole synovial membrane was in good agreement with previous studies on their action on similar types of cells as those present in synovial membranes, but originating from other tissues. All tested agents decreased MMP2 mRNA expression levels and in the case of LPS also the protein level and its activity determined by zymography, contrary to previous observations on isolated cell populations. This indicates that the response of the organized tissue is an interplay of all components and cannot be deduced from the individual reactions.     

Expression of COX-2, IL-1β, TNF-α and IL-4 in epithelium of serrated adenoma,adenoma and hyperplastic polyp

Introduction

Colon polyps and inflammatory process play the key role in neoplasia of colorectal cancer. In recent years there have been many publications on the malignancy of hyperplastic polyp (HP) which according to the WHO classification is a non-neoplastic polyp. The aim of this study is to determine the expression of inflammatory proteins COX-2, IL-1β, TNF-α and IL-4 in the epithelium of colorectal polyps.

Material and methods

In the study, 144 colorectal polyps were analyzed. The groups of HP, classical (A) and serrated adenomas (SA) and normal mucosa (control) according to histopathological studies were selected. Immunohistochemical examinations Rusing antibodies against COX-2, IL-1β, TNF-α and IL-4 were performed. The expression of analyzed protein was evaluated using modified Remmele-Stegner scale (0-16).

Results

Statistical analysis revealed higher expression of TNF-α (16 ±3.87 vs. 1 ±5.06), IL-1β (12 ±4 vs 8 ±2.72), COX-2 (9 ±2.54 vs. 8 ±3.14) and IL-4 (12 ±3.45 vs. 4 ±3.35) in SA polyps compared to the control (p < 0.001). The HP had an increased level of expression of TNF-α (12 ±3.72 vs. 1 ±5.06, p < 0.005), COX-2 (8.5 ±1.97 vs. 8 ±3.14, p < 0.012) and IL-4 (12 ±3.46 vs. 4 ±3.35, p < 0.001). Significantly higher expression of IL-4 (12 ±2.32 vs. 4 ±3.35, p < 0.001) and IL-1β (16 ±4.32 vs. 8 ±2.72, p < 0.044) in A compared to the control were observed.

Conclusions

Expression of inflammatory factors differed between polyps. Inflammation accompanied the serrated structures which occur in polyps. The inflammatory process affects the development of colorectal polyps. The HP may predispose to malignancy.     

IL-1β, IL-6 promoter,TNF-α promoter and IL-1RA gene polymorphisms and the risk of preterm delivery due to preterm premature rupture of membranes in a population of Polish women

Introduction

Our previous study revealed that anti-inflammatory cytokine gene polymorphisms increase the risk of spontaneous preterm delivery (PD) in a population of Polish women. Different genetic background of PD due to preterm premature rupture of membranes (pPROM) than PD without pPROM has been suggested. The aim of this study was to examine the relationship between the maternal carriage of polymorphic alleles of the following genes: interleukin 1β(IL-1β [+3953C>T]), interleukin 6 promoter (IL-6 [−174G>C]), tumour necrosis factor promoter (TNF-α [–308G>A]) and interleukin 1 receptor antagonist (IL-1RN) and the risk of PD caused exclusively by pPROM in a population of Polish women.

Material and methods

A case-control study. 95 Caucasian women were examined including 32 cases and 63 controls. Case subjects experienced a delivery at less than 36 weeks and 6 days of gestation due exclusively to pPROM while control subjects gave birth at term. Polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP).

Results

No statistically significant relationship between polymorphisms of examined genes and risk of PD due to pPROM in a population of Polish women was found: OR = 0.84 (95% CI: 0.34-2.01) for IL-1β, OR = 0.77 (95% CI: 0.27-2.13) for IL-6, OR = 0.72 (95% CI: 0.26-1.90) for TNF-α and OR = 1.74 (95% CI: 0.66-4.64) for IL-1RN.

Conclusions

Maternal carriage of polymorphic alleles of IL-1β, IL-6 promoter, TNF-α promoter and IL-1RA seems to have no impact on the risk of PD due to pPROM in the population of Polish women.The genetic contribution and pathomechanism of PD related to pPROM seems to differ from those of spontaneous PD without pPROM.     

High in situ mRNA levels of IL-22, TFG-β, and ARG-1 in keloid scars

Keloid scars are currently considered a chronic inflammatory process and no longer a benign skin tumor. Keloids are defined as highly inflamed, hyperproliferative pathological scars. Growth factors and cytokines have important functions in the keloid inflammatory etiopathogenesis. The aim of this study was to analyze the in situ expression of cytokines and growth factors in keloid scars in comparison with that in normal scars. Among them, we specifically assessed TGF-β, FGF, IL-33, IL-22, ARG-1, ARG-2, iNOS, VIP, VIP-R1, TAC, and TAC-R1. A total of 98 biopsies were evaluated, including of 53 keloid and 45 normal scars. The age of patients with keloids ranged from 11 to 73 years, with a mean age of 28 years and predominance of the female gender (58.5% of the total patients). Around 64.15% of the patients belonged to the black ethnic group. Evaluated keloids were most commonly located in the earlobe because of ear piercing, representing 73.6% of the cases. We found significantly greater expression of TGF-β, IL-22, and ARG-1 in keloids when compared with that in normal scars. As for IL-33, ARG-2, and VIP-R1, despite the higher number of mRNA copies found in keloids, this difference was not significant. Furthermore, FGF, iNOS, VIP, TAC, and TAC-R1 mRNA levels were not detectable, and therefore these results were inconclusive in this study. Considering these results, understanding the cellular and molecular mechanisms that control the inflammatory response during cutaneous healing may promote the development of strategies to improve the treatment of patients with keloids.     

Dialyzable Leukocyte Extract differentially regulates the production of TNFα, IL-6, and IL-8 in bacterial component-activated leukocytes and endothelial cells

Objective: To investigate i) whether the Dialyzable Leukocyte Extract (DLE) modulates the production of proinflammatory cytokines in leukocytes activated by the bacterial cell wall components lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN); ii) the effect of DLE on LPS-stimulated endothelial cells; and iii) whether the regulatory effect of DLE on inflammatory mediators is related to the modulation of Toll-like receptors (TLRs), NF-B and cAMP signaling pathways.Methods: Leukocytes were stimulated with LPS, LTA, and PGN in the presence of DLE. Endothelial cells were stimulated with LPS and treated with DLE. The levels of Tumor Necrosis Factor-(TNF), Interleukin-6 (IL-6), and IL-8 in culture supernatants were evaluated by ELISA. The expression of Toll-like receptor 2 (TLR2) and 4 (TLR4), NF-B activity and cAMP levels were evaluated by flow cytometry, EMSA, and EIA, respectively.Results: The addition of DLE to leukocytes stimulated with cell wall constituents suppressed the production of TNF. However, DLE induced IL-8 release in monocytes and enhanced IL-6 and IL-8 production by activated monocytes and endothelial cells. Also, DLE induced TLR2 and TLR4 expression, and increased cAMP levels, whereas NF-B activity was inhibited.Conclusions: The present data indicate the differential regulation by DLE of the production of TNF, IL-6, and IL-8 cytokines, associated with effects on TLR2 and TLR4 expression and NF-B and cAMP activities. We suggest a putative mechanism for the biological effects of DLE in activated leukocytes and endothelial cells.Received 3 February 2004; returned for revision 30 March 2004; accepted by M. J. Parnham 25 October 2004     

Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease of unknown aetiology. Interleukin (IL)-1β plays an important role in inflammation and has been associated with fibrotic remodelling. We investigated the balance between IL-1β and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) and serum as well as the influence of genetic variability in the IL1B and IL1RN gene on disease susceptibility and cytokine levels. In 77 IPF patients and 349 healthy controls, single nucleotide polymorphisms (SNPs) in the IL1RN and IL1B genes were determined. Serum and BALF IL-1Ra and IL-1β levels were measured using a multiplex suspension bead array system and were correlated with genotypes. Both in serum and BALF a significantly decreased IL-1Ra/IL-1β ratio was found in IPF patients compared to healthy controls. In the IL1RN gene, one SNP was associated with both the susceptibility to IPF and reduced IL-1Ra/IL-1β ratios in BALF. Our results show that genetic variability in the IL1RN gene may play a role in the pathogenesis of IPF and that this role may be more important than thought until recently. The imbalance between IL-1Ra and IL-1β might contribute to a proinflammatory and pro-fibrotic environment in their lungs.     

Comparative quantification of IL-1?, IL-10, IL-10r, TNFa and IL-7 mRNA levels in UV-irradiated human skin in vivo

OBJECTIVE AND DESIGN: Ultraviolet (UV) exposure induces local immunosuppression and inflammation in human skin. Cytokines are, in part, responsible for these responses. To investigate the effects of UV-induced gene expression at the molecular level we established a sensitive in vivo/ex vivo method for a comparative quantification of cytokines and receptors involved in the local skin immune reactions. MATERIAL AND METHODS: Specific mRNA levels of human UV-irradiated skin were determined by real time quantification (TaqMan RT-PCR). Highly efficient PCR-reaction conditions were obtained by designing very short PCR-templates (72-87 bp). The most sensitive PCR-conditions were obtained by optimisation of primer and Mn(OAc)2-concentrations, which led to significant PCR signals (C(T)-value) of less than 36 cycles. A strong correlation between PCR efficiency of the internal control (GAPDH) compared to targets (IL-1beta, IL-10, IL-10r, TNFalpha, IL-7) allowed the use of deltadelta C(T)-method to quantify comparable mRNA levels. RESULTS: Interleukin-1beta (IL-1beta), Interleukin-10 (IL-10), and tumour necrosis factor alpha (TNFalpha) mRNA levels were increased in a time- and dose-dependent manner. Interleukin-1beta induction reached a maximum (approx. 44-fold) 6 h after a UV-dose equivalent to 3 times the minimal erythemal doses just perceptible (MEDjp). Maximal TNFalpha mRNA expression (approx. 14-fold) was also detected 6 h after UV exposure. Interleukin-10 mRNA induction reached a maximum of approximately 14-fold 24 h after UV-irradiation of 3 MEDjp. Time- and dose-dependent changes in Interleukin-7 and Interleukin-10 receptor mRNA levels did not occur after UV-irradiation. CONCLUSIONS: Time-distinct gene induction of IL-1beta, TNFalpha and IL-1beta is involved in UV-induced immune reactions, but no considerable changes were found for IL-10r or IL-7.     

Differential susceptibility to lethal endotoxaemia in mice deficient in IL-1α, IL-1β or IL-1 receptor type I

Joosten LAB, van de Veerdonk F, Vonk AG, Boerman OC, Keuter M, Fantuzzi G, Verschueren I, van der Poll T, Dinarello CA, Kullberg BJ, Van der Meer JWM, Netea MG. Differential susceptibility to lethal endotoxaemia in mice deficient in IL‐1α, IL‐1β or IL‐1 receptor type I. APMIS 2010; 118: 1000–7. The role of intereukin‐1 (IL‐1) in mortality caused by endotoxaemia remains controversial. While IL‐1 receptor antagonist (IL‐1Ra) protects mice from lethal endotoxaemia, mice deficient in IL‐1β (IL‐1β^{? /?}) display normal susceptibility to lipopolysaccharide (LPS). The aim of this study was to identify the source of these discrepancies. Mice deficient in IL‐1α, IL‐1β or IL‐1R type I were injected intraperitoneally with Escherichia coli or Salmonella typhimurium LPS. Survival of the mice was examined and compared with C57/Bl6 wild‐type mice. In addition, serum cytokine concentrations were determined after LPS challenge and in vitro cytokine production by peritoneal macrophages was analysed. Clearance of radioactive IL‐1α was examined in IL‐1α^?/? and wild‐type mice. IL‐1β^?/? mice were normally susceptible to endotoxaemia and cytokine production did not differ from that in control mice. Surprisingly, LPS mortality in IL‐1α^?/? mice was significantly greater than that in control mice, accompanied by higher interferon‐γ release. These effects were mediated by a distorted homeostasis of IL‐1RI receptors, as shown by a strongly delayed clearance of IL‐1α. In contrast to the IL‐1α^?/? and IL‐1β^?/? mice, IL‐1RI^?/? mice were completely resistant to high doses of LPS. In conclusion, IL‐1RI‐mediated signals are crucial in mediating mortality occurring as a result of lethal endotoxaemia. Investigation of IL‐1‐mediated pathways in IL‐1 knock‐out mice is complicated by a distorted homeostasis of IL‐1Rs.     

Association of IL-1β, IL-1Ra and FABP1 gene polymorphisms with the metabolic features of polycystic ovary syndrome

Background

Polycystic ovary syndrome (PCOS), a highly prevalent endocrinopathy is currently being designated as chronic low grade inflammatory state. IL-1β, IL-1Ra and FABP1 are critical mediators of inflammatory processes and are speculated to play a role in the pathogenesis of PCOS. The aim of this study was to study the association of IL-β, IL-1Ra and FABP1 gene polymorphisms with PCOS and related metabolic features.

Subjects

95 PCOS and 45 age matched healthy control subjects were enrolled in this study.

Methods

Polymorphism in genes IL-1β, IL-1Ra and FABP1 was studied by PCR, PCR–RFLP and sequencing methods, respectively. Hormonal and lipid profiles were evaluated for all the subjects.

Results

Hormonal and lipid profiles showed significant differences between PCOS and control subjects. Allele and genotype frequencies of IL-1β, IL-1Ra and FABP1 gene polymorphisms did not vary between the control and PCOS group. However, T allele of C[-511]T variant of IL-1β, allele II in intron 2 of IL-1Ra and A allele of A/G variant of FABP1 (rs2197076) showed significant association with many metabolic features associated with PCOS.

Conclusions

Polymorphism in genes encoding cytokines and proteins involved in lipid metabolism can provide insights into the genetics of the disease and may contribute to assess the associated risk of cardiovascular diseases (CVD), dyslipidemia and metabolic syndrome (MetS) associated with PCOS.

     

Modification of in Vivo and in Vitro TNF-α, IL-1, and IL-6 Secretion by Circulating Monocytes During Hyperbaric Oxygen Treatment in Patients with Perianal Crohn's Disease

Treatment of perianal inflammatory lesions in Crohn's disease (CD) is unsatisfactory and novel treatment modalities are pursued. We have recently reported a good clinical effect of hyperbaric oxygen (HBO) treatment in perianal CD. In the present study, seven patients with perianal CD were subjected to daily sessions of HBO in a multiplace hyperbaric chamber. Each patient received a total of 20 sessions during a time period of 1 month, and IL-1, IL-6, and TNF- measurements were done several times during the initial sessions and after completing therapy. Pretreatment cytokine levels were elevated in patients compared to age-matched 10 normal controls. During the first 7 days of treatment, IL-1, IL-6, and TNF- levels in supernatants of LPS-stimulated monocytes derived from patients' peripheral blood were decreased compared to pretreatment levels. Parallel measurements of serum IL-1 levels revealed an initial elevation and thereafter decreased levels, which remained low throughout the first week of HBO treatment. After completion of therapy, cytokine levels increased to pretreatment values. We conclude that alterations in secretion of IL-1, IL-6, and TNF- may be related to the good clinical effect of HBO treatment in CD patients with perianal disease.     

Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide,IL-1β, TNF-α and IL-6 in an in-vitro model of brain inflammation

Background  

Brain inflammation plays a central role in multiple sclerosis (MS). Dimethylfumarate (DMF), the main ingredient of an oral formulation of fumaric acid esters with proven therapeutic efficacy in psoriasis, has recently been found to ameliorate the course of relapsing-remitting MS. Glial cells are the effector cells of neuroinflammation; however, little is known of the effect of DMF on microglia and astrocytes. The purpose of this study was to use an established in vitro model of brain inflammation to determine if DMF modulates the release of neurotoxic molecules from microglia and astrocytes, thus inhibiting glial inflammation.     

Serum levels of TGFβ, IL-10, IL-17, and IL-23 cytokines in β-thalassemia major patients: the impact of silymarin therapy

Several immunological abnormalities have been characterized in β-thalassemia, many of which are linked to or identified with cytokines. In this study, we investigated the serum levels of TGF-β, IL-10, IL-17 and IL-23 in β-thalassemia major patients in comparison with healthy controls. The immunomodulatory effect of silymarin (a flavonoid complex obtained from Silybum marinum) on the serum levels of cytokines was further evaluated in thalassemia patients receiving silymarin (420?mg/day) and compared with patients treated with placebo for 6-month. Serum cytokines levels were measured by enzyme linked immunosorbent assay (ELISA). The results showed a significant higher concentration of TGF-β and IL-23 in the patient group than control group. Among studied cytokines, a significant reduction in serum IL-10 levels was found in patients treated with silymarin when compared with IL-10 values at baseline. However, no significant difference was observed between baseline values of cytokine compared with end values in placebo group. Our data suggest the presence of imbalanced immune condition involving inflammation and immunosuppression in thalassemia patients, which could be modulated to a more effective immune response by silymarin.     

Differential regulation of TNFα, IL-1β, IL-6, IL-8, TNFβ, and IL-10 by pentoxifylline

Pentoxifylline (PTX) is a methylxanthine drug known to inhibit the production of tumor necrosis factor-alpha (TNFα), which plays a key role in inflammation. Recent studies also revealed that other cytokines may be inhibited by PTX. We investigated PTX effects on production and mRNA expression of TNFα, IL-1β, IL-6, IL-8, TNFβ and IL-10. Cytokine release was studied in 1/10 diluted whole blood culture (WB) and in peripheral blood mononuclear cell (PBMC) culture. Cytokine production was triggered in both culture systems by endotoxin (LPS) or by phorbol ester (PMA) plus phytohemagglutinin (PHA). Our results showed that expression and production of TNFα and TNFβ were inhibited by PTX in a dose-dependent manner. Moreover, we observed that depending on the way of activating cells, PTX induced an up- or a down-regulation (in PMA+PHA or LPS stimulated cells, respectively) for IL-1 and IL-6 release. We also noted that the effects of PTX on IL-6, IL-8 and IL-10 production were different in WB and in PBMC culture. In conclusion PTX acts on cytokine in a complex manner depending on cellular environment and on the method of activation.