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.     

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.     

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.

     

Evaluation of serum levels of IL-6, TNF-α, IL-10, IL-2 and IL-4 in patients with chronic hepatitis

Background

Changes in various cytokine activities have been reported during both HBV and HCV infections, while an imbalance of pro-inflammatory and anti-inflammatory cytokine production influences their immunopathogenesis. The aims of the present study are (a) to measure serum levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-10 (IL-10), interleukin-2 (IL-2) and interleukin-4 (IL-4) in a sample of patients affected either by chronic HBV infection or by chronic HCV infection and in healthy controls (b) to correlate serum levels of IL-6, TNF-α, IL-10, IL-2 and IL-4 with biochemical markers of liver disease and (c) to evaluate differences of the aforementioned cytokines between HBV and HCV patients, as well as between patients and healthy controls.

Methods

The study population consisted of 50 patients with chronic hepatitis B, 40 patients with chronic hepatitis C and 30 healthy controls aged between 28 and 75 years. Biochemical markers of liver disease were evaluated by routine methods approved by IFCC. Serum concentrations of IL-6, TNF-α, IL-10, IL-2 and IL-4 were determined with the Human Cytokine/Chemokine Panel I Merck Millipore.

Results

HBV patients showed statistically significant difference in TNF-α and IL-2 levels, versus healthy controls. HCV patients showed statistically significant difference in TNF-α, IL-10 and IL-2 levels versus healthy controls. IL10 and IL-2 levels were significantly different between HBV and HCV patients.

Conclusions

This study evaluated the serum cytokine levels (IL-6, TNF-α, IL-10, IL-2 and IL-4) of chronic hepatitis B or C patients, as well as the differences in such levels between patients and healthy controls. Correlations of cytokine levels with biochemical markers of liver disease were also observed, reflecting the degree of activity of the inflammatory process in the liver.     

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.     

冠心病患者TNF-α,IL-1β,IL-6,IL-8的变化研究

目的 :对冠心病患者血清中肿瘤坏死因子 (TNF -α)、白介素 - 1β(IL - 1β)、白介素 - 6 (IL - 6 )、白介素 - 8(IL - 8)含量进行分析 ,以探讨它们在冠心病发病过程中的意义。方法 :研究对象为正常对照组 36例 ,稳定型心绞痛组 32例 ,心肌梗塞组 39例 ,采用化学发光酶分析法检测其血清TNF -α、IL - 1β、IL - 6、IL - 8水平。结果 :与正常组比较 ,冠心病患者中TNF -α、IL - 1β、IL - 6、IL - 8水平均有不同程度升高 ,尤以心肌梗塞组升高明显 ,其差别有显著临床意义。心绞痛组TNF -α(p <0 0 5 ) ,IL - 6 (p <0 0 1) ,IL - 8(p <0 0 5 )。心肌梗塞组TNF -α(p<0 0 1) ,IL - 1β(p<0 0 5 ) ,IL - 6 (p <0 0 0 1) ,IL - 8(p <0 0 0 1)。 结论 :TNF -α、IL - 1β、IL - 6、IL- 8与动脉粥样硬化和冠心病的发生有密切关系 ,这些细胞因子可通过相互诱导、相互协同共同参与冠心病的发生、发展过程     

Discoordinate expression of IL-1α and IL-1β in interfacial membranes of failed joint prostheses

Bone resorption following either cemented or uncemented total hip replacement has been implicated as an important etiologic factor in aseptic loosening of prostheses, the most frequent cause of clinical failure. Interleukin-1 (IL-1), collagenase and prostaglandin E₂ are considered to play key roles in pathological bone resorption. We have measured the actual levels and quantified the genes coding for several cytokines [IL-1, IL-1, IL-4, IL-6, platelet-derived growth factors (PDGF), transforming growth factor- (TGF) and tumor necrosis factor- (TNF)] in interfacial membranes obtained from cemented or uncemented loosened joint replacements. IL-1, IL-6 and TNF were barely detectable in the interfacial membranes either at protein or mRNA levels, while IL-1 and TGF were found to be expressed at the highest levels in freshly isolated tissues. However, the expression of IL-1 increased 10–1000-fold either in isolated cells or explant cultures of interfacial membranes within 24 h. The expression of other cytokines, measured directly in tissue or cells, did not suggest a discoordinate expression of bone-resorbing cellular mediators.     

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.     

Expression of IL-1α, IL-6, TGF-β, FasL and ZNF265 During Sertoli Cell Infection by Ureaplasma Urealyticum

To investigate immunoregulatory mechanisms of Sertoli cells in the testis in vitro and in vivo, we utilized our well-characterized Ureaplasma Urealyticum （UU）-induced model. We investigated the expressions of IL-1α, IL-6, TGF-β, FasL and ZNF265 at the first, second and third weeks post-infection. During recovery from inflammation and with the help of negative regulators TGF-β and FasL, the high levels of IL-1α and IL-6 expressions were observed in the early stages of the infection, and decreased gradually in the later weeks both in vitro and in vivo. The trend of varied expression of ZNF265 was similar to those of TGF-β and FasL in vitro and in vivo for Sertoli cells infected with UU.     

Expression of IL-1α, IL-6, TGF-β, FasL and ZNF265 During Sertoli Cell Infection by Ureaplasma Urealyficum

To investigate immunoregulatory mechanisms of Sertoli cells in the testis in vitro and in vivo, we utilized our well-characterized Ureaplasma Urealyticum (UU)-induced model. We investigated the expressions of IL-1α, IL-6,TGF-[3, FasL and ZNF265 at the first, second and third weeks post-infection. During recovery from inflammation and with the help of negative regulators TGF-[3 and FasL, the high levels of IL-1α and IL-6 expressions were observed in the early stages of the infection, and decreased gradually in the later weeks both in vitro and in vivo.The trend of varied expression of ZNF265 was similar to those of TGF-β and FasL in vitro and in vivo for Sertoli cells infected with UU. Cellular & Molecular Immunology. 2009;6(3):215-221.     

Immunohistochemical expression of proinflammatory cytokines IL-1β, IL-6, TNF-α and involvement of COX-2, quantitatively confirmed by Western blot analysis, in Wernicke's encephalopathy

Selective cerebral vulnerability is a major consequence of Wernicke's encephalopathy (WE), in which focal areas of the brain exhibit symmetrical profound neuronal loss and accompanying gliosis, occurring most frequently in diencephalic regions such as the thalamus and the mammillary bodies. Many processes have been proposed to explain the selective cerebral vulnerability and the focal neuronal cell death in Wernicke's encephalopathy. There are several mechanisms which are common to the pathophysiology of encephalopathies caused by thiamine deficiency (TD). Recently, emphasis is being placed on deficit in mitochondrial oxidative metabolism, oxidative/nitrosative stress, and the release of proinflammatory cytokines such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α). Cyclooxygenase-2 (COX-2) plays major roles in regulating brain damage and inflammation.Here we present two fatal cases of non-alcohol associated WE. The immunohistochemical study revealed increased proinflammatory cytokine immunoreactivity in the neurons of the mammillary bodies and medial thalamus, and in the periaqueductal regions, compared with basal constitutive levels of expression in the frontal cortex. Positive (WE cases) and negative (immediate trauma deaths) case-controls were used to confirm the results. TD induced IL-1β proteins weakly, while moderate increase was observed for TNF-α and IL-6. Immunofluorescence analysis by confocal microscopy confirmed the staining results for immunoreactivity in WE brains. Further, the induction of proinflammatory cytokine protein expression levels was quantified by Western blot analysis.     

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.     

Serum Levels of IL-6, IL-10, IL-12, IL-17 and IFN-γ and Their Association with Markers of Bone Metabolism in Vitamin D-Deficient Female Students

Different studies have shown the regulatory effects of vitamin D₃ on the immune system and bone metabolism. Regarding the effects of vitamin D on immune cells and the importance of cytokines on bone metabolism, we assessed the association between serum levels of interleukin (IL)-6, IL-10, IL-12, IL-17 and IFN-γ cytokines and bone metabolism markers (Ca, P, PTH, ALP) in female students with vitamin D deficiency compared with control group. A total of 100 subjects with 25-hydroxy vitamin D₃ (25-(OH) D₃) deficiency were selected as case and 100 subjects with sufficient 25-hydroxy vitamin D₃ (25-(OH) D₃) were selected as the control group. The serum levels of IL-6, IL-10, IL-12, IL-17 and IFN-γ were measured by ELISA method. Ionized Ca, PTH, P, ALP levels were also determined in all participants. The results showed a statistically significant positive correlation between the levels of ALP with IFN-γ, PTH with IL-17 and a significant negative correlation between P with IL-10 in vitamin D deficient group. The results suggest that IL-17, IFN-γ and IL-10 are important mediators of bone metabolism and vitamin D affect bone metabolism, at least in part, through immune system. In addition, not only vitamin D affect bone metabolism but also modulates immune responses.     

IL-1可诱导产生IL-1

白细胞介素1(IL-1)作为炎症介质近来引起了人们的关注。据Dinarello等人报道,用IL-1可以诱发IL-1的产生。他们给家兔注射大量的重组IL-1α,以便观察双峰性发热现象。大约注射后3小时出现发热的第二峰,推测这就是由内源性产生的IL-1所致。用此时引起发热的血清再诱导其他家兔发热,在血清中分子量为30～40KD以及15KD的组份中可发现     

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.     

Enhancement of in vivo production of IL-1α and IL-6 in mice by Y-25510, a 1H-pyrazolo[3,4-b]pyridine-1-acetic acid derivative

The serum concentrations of interleukin(IL)-lα and IL-6 in C57BL/6 and C3H/HeN mice reached the maximum at 12–16h after the intravenous treatment with (±)-3-[4-(2-dimethylamino-l-methylethoxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-1-acetic acid (Y-25510) at a dose of 3 mg/kg, and the concentration of IL-10 did at 20h after the treatment. By repeated treatments with Y-25510 to C57BL/6 mice for 14 days, the maximal values of IL-lα and IL-6 at day 14 were respectively 6.6 times and 5.7 times relative to those on day 1. Neither the counts of peripheral leukocytes nor those of platelets were, however, increased until day 15. The repeated treatment with Y-25510 followed by anti-IL-10 antibody for 14 days was significantly more effective than that with Y-25510 alone in increasing the concentrations of IL-lα and IL-6 in C3H/HeN mice. In addition, both the counts of peripheral leukocytes and platelets were significantly increased at day 18. In conclusion, Y-25510 enhanced not only the production of endogenous IL-1α and IL-6 but also that of IL-10 in healthy mice. As a result, in normal conditions, both the counts of peripheral leukocytes and platelets were never increased because of the inhibitory effect of endogenously produced IL-10.     

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.     

Effect of peptide aldehydes with IL-1β converting enzyme inhibitory properties on IL-1α and IL-1β production in vitro

Tripeptide and pentapeptide aldehydes as substrate-base inhibitors of cysteine proteases were designed in our laboratory for the inhibition of interleukin-lβ converting enzyme (ICE), a recently described cysteine protease responsible for the processing of IL-1β. The biological effectivity of the peptide aldehydes was studied in THP-1 cells and human whole blood. The released and cell-associated IL-1α and IL-1β levels were determined by ELISA from the supernatants and cell lysates, respectively. The total IL-1 like bioactivity was assayed by the D₁₀G₄₁ cell proliferation method. The tripeptide aldehyde (Z-Val-His-Asp-H) and pentapeptide aldehyde (Eoc-Ala-Tyr-Val-Ala-Asp-H) significantly reduced IL-1β levels in the supernatants in relatively high concentrations (10–100 μM), but the IL-1α release was unaffected by these peptides. However, a considerable decrease in the cell-associated IL-1β and IL-1α levels was observed. N-terminal extension of the tripeptide aldehyde yielded even more potent inhibitors. Amino acid substitution at the P₂ position did not cause considerable changes in the inhibitory activity. The peptide aldehydes suppressed the IL-1β production in a reversible manner, whereas dexamethasone, a glucocorticoid, had a prolonged inhibitory effect. The inhibitory effect of these peptides and that of dexamethasone appeared to be additive. These findings indicate that these peptide aldehydes might be used as IL-β inhibitory agents in experimental models in which IL-1β is a key mediator or ICE is implicated.