Influence Of IL-1β Research Articles

Quantification and Influence of IL-1β on Pain and Inflammatory Response after Placement of a Cement-Screw-Retained Restoration.

Background: The objective of this study was to evaluate the pain and inflammatory response in soft tissues using healing and prosthetic abutments of different diameters and lengths. Methods: The study population was rehabilitated with Astra Tech EV single implants (Dentsply Sirona, Atlantis, Dentsply Sirona S.A., Barcelona, Spain) of 4.2 and 4.8 millimetres in diameter in the upper and lower maxilla and loaded with custom abutments digitally designed using Dentsply Sirona's Virtual Atlantis Design software (Atlantis WebOrder, Dentsply Sirona S.A., Barcelona, Spain), version 4.6.5. The custom abutments had a larger diameter than the healing abutments to evaluate for biomarkers through ELISA. Results: Rehabilitations in the mandible and with healing abutments with diameters less than 4.29 mm and rehabilitators with diameters less than 2.18 mm elicited a higher pain and inflammatory response and, in turn, higher interleukin-1β values. Conclusions: Greater inflammation was evident in cases in which healing abutments with reduced diameter were used compared to the same subsequent rehabilitation with prosthetic abutments with larger diameters.

Development of Therapeutic Agent for Osteoarthritis via Inhibition of KIAA1199 Activity: Effect of Ipriflavone In Vivo.

This study aimed to clarify the effects of ipriflavone, which effectively reduces KIAA1199 activity, on osteoarthritis (OA) development and progression in an in vivo OA mouse model. The OA model mice were divided into the ipriflavone (200 mg/kg/day) group and the control group. OA onset and progression were evaluated with the Mankin score, and KIAA1199 expression and hyaluronan (HA) accumulation were analyzed by immunostaining. The molecular weight of HA in the cartilage tissue and serum HA concentration were analyzed by chromatography and competitive HA enzyme-linked immunoassay. The effects of ipriflavone on the bovine cartilage explant culture under the influence of IL-1β were also investigated. In the ipriflavone group, Safranin-O stainability was well-preserved, resulting in significant reduction of the Mankin score (p = 0.027). KIAA1199 staining positivity decreased and HA stainability was preserved in the ipriflavone group. The serum HA concentration decreased, and the molecular weight of HA in the cartilage tissue increased in the ipriflavone group. The results of the cartilage explant culture indicated that ipriflavone could reduce GAG losses and increase the molecular weight of HA. Thus, ipriflavone may have an inhibitory effect on OA development/progression. Ipriflavone could be a therapeutic drug for OA by targeting KIAA1199 activity.

IL-1β strengthens the physical barrier in gingival epithelial cells

ABSTRACT Periodontitis is one of the most common oral diseases worldwide and is caused by a variety of interactions between oral bacteria and the host. Here, pathogens induce inflammatory host responses that cause the secretion of proinflammatory cytokines such as IL-1β, IL-6, and IL-8 by oral epithelial cells. In various systems, it has been shown that inflammation compromises physical barriers, which enables bacteria to invade the tissue. In this study, we investigated the barrier properties of the oral mucosa under physiological and inflamed conditions. For this purpose, we assessed the influence of IL-1β on the transepithelial electrical resistance and in particular on tight junctions in vitro in human stratified squamous epithelium models. Indirect immunofluorescence and western blot analyses were performed to investigate localization and expression of tight junction proteins in primary gingival cells, immortalized gingival cells and native gingiva. Furthermore, the TEER of gingival keratinocytes was assessed. The results showed that IL-1β led to strengthening of the gingival keratinocyte barrier. This was demonstrated by an increase in TEER, the upregulation of TJ proteins, and an increase in the formation of TJ strands. The IL-1β-mediated upregulation of occludin was prevented by the NF-κB inhibitor BAY 11–7085. These observations provide insights into host responses in the early stages of periodontal disease and offer information about TJ formation in human gingival epithelial cells under physiological and inflammatory conditions. Comprehensive knowledge of the physical barrier during inflammation may help in developing strategies to effectively target the inflammatory barrier to improve the bioavailability of drugs for the treatment of periodontitis.

Influence of IL-1β, STAT3 & 5 and TLR-5 gene polymorphisms on rheumatic heart disease susceptibility in north Indian population

BackgroundRheumatic heart disease (RHD) is the most serious complication of heart that comprises inflammatory reactions in heart valves. Many studies have demonstrated the contribution of host genetic factors in susceptibility to RHD and many cytokine gene variants have been linked with susceptibility to RHD. We sought to determine the role of genetic variants in IL-1β, STAT3, STAT5B and TLR5 genes in conferring risk of RHD in two cohorts of RHD patients. MethodsThe study included 400 echocardiography confirmed RHD patients and 300 controls from North Indian Population. We categorized RHD patients into two sub-groups based on involvement of heart valves, mitral valve lesion alone (MVL), and combined valve lesions including mitral valve (CVL). Genotyping for all the polymorphisms was done using TaqMan /PCR-RFLP methods. ResultsOur results showed that the genotypic frequencies of IL-1β, STAT3, STAT5B andTLR5 genes polymorphisms were significantly associated with RHD risk. To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings with RHD risk. In subgroup analysis, STAT3 polymorphism remained significant with MVL in RHD patients. ConclusionIL-1β, STAT3, STAT5B and TLR5 genes polymorphism may be useful markers for the identification of individuals with high risk of RHD in the susceptible population.

In vivo effects of GnRH on expression of interleukin 1 (IL-1) system members in bovine preovulatory follicles and the influence of IL-1β on cumulus-oocyte complexes cultured in vitro

Abstract The purpose of this study was to determine the effects of in vivo GnRH treatment on mRNA expression of IL-1β system in bovine granulosa cells from preovulatory follicles and to analyze the in vitro effect of gonadotropins on the IL-1β system gene expression in cumulus cells. Moreover, the additive effect of IL-1β on cumulus expansion, gene expression and ultrastructural integrity of COCs cultured in vitro was evaluated. In vivo studies in granulosa cells demonstrated that IL-1RA mRNA levels were increased after 24 h of GnRH treatment. Similarly, the presence of gonadotropins increased the levels of mRNAs for IL-1R1 and IL-1RA in cumulus cells after 24 h of culture in vitro. The presence of IL-1β in culture medium did not influence cumulus expansion, but it increased the expression of mRNAs for IL-1β, IL-1RA, HAS2 and iNOS after COC culture. In addition, the ultrastructure of COCs cultured in vitro in the presence of IL-1β was maintained. In conclusion, IL-1RA mRNA is upregulated in granulosa cells at later stages of the ovulatory process in cattle. In cumulus cells, mRNA expression of IL-1RI and IL-1RA is induced by gonadotropins and IL-1β maintains the ultrastructure of COC cultured in vitro.

Interleukin-1β induces an inflammatory response and the breakdown of the endothelial cell layer in an improved human THBMEC-based in vitro blood–brain barrier model

The blood-brain barrier is necessary to provide an optimal environment for cerebral function. It consists of endothelial cells that interact through interendothelial tight junctions and form a barrier with low permeability. Therefore, the infiltration of lymphocytes into the central nervous system is limited. Pathological conditions, such as chronic-inflammatory diseases and viral infections, induce a breakdown in the blood-brain barrier, which facilitates the accumulation of immune cells in the brain. Using the endothelial cell line "transfected human brain microvascular endothelial cells", we established an improved in vitro blood-brain barrier model. Using interleukin-1β, we refined this model into an inflammatory blood-brain barrier model. The model is characterised by a transendothelial electrical resistance of 250 Ohm cm(2) and a permeability coefficient of 1×10(-6) cm/s for sodium fluorescein. IL-1β induces a strong inflammatory response, resulting in the increased expression of the adhesion molecule ICAM-1 and the pro-inflammatory cytokines IL-6, IL-8, and TNFα. Furthermore, the transendothelial electrical resistance decreased and the paracellular permeability increased in the presence of IL-1β. Additionally, the expression of the tight junction protein ZO-1 was reduced. As a consequence, an increased number of leukocytes were able to cross the cell layer. The model presented here exhibits improved characteristics with regards to TEER and permeability. The influence of IL-1β has not been described before in this model system. The inflammatory in vitro blood-brain barrier model provides a useful tool for studying inflammatory processes at the blood-brain barrier, especially processes provoked by IL-1β.

The Influence of Nuclear Magnetic Resonance Therapy (NMRT) and Interleukin IL1-β Stimulation on Cal 78 Chondrosarcoma Cells and C28/I2 Chondrocytes

The Influence of Nuclear Magnetic Resonance Therapy (NMRT) and Interleukin IL1-β Stimulation on Cal 78 Chondrosarcoma Cells and C28/I2 Chondrocytes

Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts

Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth.

Human CCR6+CXCR3+ “Th1/17” cells are polyfunctional and can develop from Th17 cells under the influence of IL-1β and IL-12 (P4122)

Abstract In humans, memory CD4+ T cells co-expressing the chemokine receptors CCR6 and CXCR3, and producing both IL-17 and IFN-γ, have been proposed to be highly pathogenic in several autoimmune disorders. However, their developmental pathways, relationship with “classic” Th17 and Th1 cells and physiological role in normal immune responses are not well understood. Here, we examined CCR6+CXCR3+ T cells from healthy individuals, and found that ex vivo those cells expressed higher levels of IL12Rβ2 and IL23R compared to Th17 and Th1 cells and displayed an enhanced response to IL-12 and IL-23. Interestingly, Th17 cells cultured in the presence of IL-1β upregulated IL-12Rβ2, and IL-1β together with IL-12 induced IL-17+ IFN-γ+ cells and strongly increased the expression of T-bet, IL-12Rβ2 and IL-23R without inhibiting RORγt. CCR6+CXCR3+ T cells shared antigen specificities with Th17 and Th1 cells, and T cells specific for extracellular bacteria such as S. pneumoniae, E. coli and L. rhamnosus were highly enriched in this subset. Furthermore, a significant proportion of CCR6+CXCR3+ T cells expressed the gut-homing molecule α4β7. Thus, CCR6+CXCR3+ CD4+ T cells are a functionally distinct population of T cells with broad antigen specificity and migratory potential that can develop from “classic” Th17 cells under the influence of IL-1β and IL-12. Further characterization of these cells will reveal new insights into CD4+ T cell differentiation and function in infection and autoimmunity.

The influence of IL-1β, TNFα and IL-6 on induction of apoptosis in cultured porcine luteal cells

The influence of IL-1β, TNFα and IL-6 on induction of apoptosis in cultured porcine luteal cells

Interleukin-1 beta and tumor necrosis factor alpha inhibit migration activity of chondrogenic progenitor cells from non-fibrillated osteoarthritic cartilage

IntroductionThe repair capability of traumatized articular cartilage is highly limited so that joint injuries often lead to osteoarthritis. Migratory chondrogenic progenitor cells (CPC) might represent a target cell population for in situ regeneration. This study aims to clarify, whether 1) CPC are present in regions of macroscopically intact cartilage from human osteoarthritic joints, 2) CPC migration is stimulated by single growth factors and the cocktail of factors released from traumatized cartilage and 3) CPC migration is influenced by cytokines present in traumatized joints.MethodsWe characterized the cells growing out from macroscopically intact human osteoarthritic cartilage using a panel of positive and negative surface markers and analyzed their differentiation capacity. The migratory response to platelet-derived growth factor (PDGF)-BB, insulin-like growth factor 1 (IGF-1), supernatants obtained from in vitro traumatized cartilage and interleukin-1 beta (IL-1β) as well as tumor necrosis factor alpha (TNF-α) were tested with a modified Boyden chamber assay. The influence of IL-1β and TNF-α was additionally examined by scratch assays and outgrowth experiments.ResultsA comparison of 25 quadruplicate marker combinations in CPC and bone-marrow derived mesenchymal stromal cells showed a similar expression profile. CPC cultures had the potential for adipogenic, osteogenic and chondrogenic differentiation. PDGF-BB and IGF-1, such as the supernatant from traumatized cartilage, induced a significant site-directed migratory response. IL-1β and TNF-α significantly reduced basal cell migration and abrogated the stimulative effect of the growth factors and the trauma supernatant. Both cytokines also inhibited cell migration in the scratch assay and primary outgrowth of CPC from cartilage tissue. In contrast, the cytokine IL-6, which is present in trauma supernatant, did not affect growth factor induced migration of CPC.ConclusionThese results indicate that traumatized cartilage releases chemoattractive factors for CPC but IL-1β and TNF-α inhibit their migratory activity which might contribute to the low regenerative potential of cartilage in vivo.

Role of interleukin-1β in the regulation of porcine corpora lutea during the late luteal phase of the cycle and during pregnancy

Interleukin-1β (IL-1β) may regulate ovarian physiology. In this study, the influence of IL-1β on secretory activity within the corpora lutea (CL) of cyclic and gravid pigs was determined in vitro during different stages of the CL lifespan, e.g. on Days 10-11, 12-13 and 15-16 of the oestrous cycle and pregnancy. IL-1β (10 ng/ml) increased prostaglandin E2 (PGE2) secretion from CL of the cyclic and gravid pigs during studied days of the oestrous cycle and pregnancy. Increase (P < 0.05) of prostaglandin F2α (PGF2α) in IL-1β-treated CL was demonstrated only on Days 10-11 of the oestrous cycle. More potent stimulatory effect of IL-1β on PGE2 than PGF2α secretion resulted in the enhancement of the PGE2:PGF2α ratio in cyclic and early pregnant CL. IL-1β increased (P < 0.05) progesterone (P4) secretion only in gravid CL and had no effect on oestradiol-17β (E2) release. Expression of cyclooxygenase-2 (COX-2) mRNA was stimulated (P < 0.05) in IL-1β-treated cyclic and gravid CL. Expression of prostaglandin synthase mRNAs in response to IL-1β did not increase. In conclusion, IL-1β modulates PGE2, PGF2α and P4 secretion from porcine CL, depending on luteal stage and the surrounding hormonal milieu. The cytokine may act locally in porcine CL for luteotrophic support throughout the PGE2-mediated synthesis and secretion.

MicroRNA-101 Regulates Amyloid Precursor Protein Expression in Hippocampal Neurons

The amyloid precursor protein (APP) and its proteolytic product amyloid beta (Abeta) are associated with both familial and sporadic forms of Alzheimer disease (AD). Aberrant expression and function of microRNAs has been observed in AD. Here, we show that in rat hippocampal neurons cultured in vitro, the down-regulation of Argonaute-2, a key component of the RNA-induced silencing complex, produced an increase in APP levels. Using site-directed mutagenesis, a microRNA responsive element (RE) for miR-101 was identified in the 3'-untranslated region (UTR) of APP. The inhibition of endogenous miR-101 increased APP levels, whereas lentiviral-mediated miR-101 overexpression significantly reduced APP and Abeta load in hippocampal neurons. In addition, miR-101 contributed to the regulation of APP in response to the proinflammatory cytokine interleukin-1beta (IL-lbeta). Thus, miR-101 is a negative regulator of APP expression and affects the accumulation of Abeta, suggesting a possible role for miR-101 in neuropathological conditions.

Crohn’s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn’s disease

Traditionally, Crohn’s disease has been associated with a Th1 cytokine profile, while Th2 cytokines are modulators of ulcerative colitis. This concept has been challenged by the description of tolerising regulatory...

IFN-gamma Impairs Release of IL-8 by IL-1beta-stimulated A549 Lung Carcinoma Cells

BackgroundProduction of interferon (IFN)-γ is key to efficient anti-tumor immunity. The present study was set out to investigate effects of IFNγ on the release of the potent pro-angiogenic mediator IL-8 by human A549 lung carcinoma cells.MethodsA549 cells were cultured and stimulated with interleukin (IL)-1β alone or in combination with IFNγ. IL-8 production by these cells was analyzed with enzyme linked immuno sorbent assay (ELISA). mRNA-expression was analyzed by real-time PCR and RNase protection assay (RPA), respectively. Expression of inhibitor-κ Bα, cellular IL-8, and cyclooxygenase-2 was analyzed by Western blot analysis.ResultsHere we demonstrate that IFNγ efficiently reduced IL-8 secretion under the influence of IL-1β. Surprisingly, real-time PCR analysis and RPA revealed that the inhibitory effect of IFNγ on IL-8 was not associated with significant changes in mRNA levels. These observations concurred with lack of a modulatory activity of IFNγ on IL-1β-induced NF-κB activation as assessed by cellular IκB levels. Moreover, analysis of intracellular IL-8 suggests that IFNγ modulated IL-8 secretion by action on the posttranslational level. In contrast to IL-8, IL-1β-induced cyclooxygenase-2 expression and release of IL-6 were not affected by IFNγ indicating that modulation of IL-1β action by this cytokine displays specificity.ConclusionData presented herein agree with an angiostatic role of IFNγ as seen in rodent models of solid tumors and suggest that increasing T helper type 1 (Th1)-like functions in lung cancer patients e.g. by local delivery of IFNγ may mediate therapeutic benefit via mechanisms that potentially include modulation of pro-angiogenic IL-8.

Interleukin-1β interferes with signal transduction induced by neurotrophin-3 in cortical neurons

It was previously observed that IL-1β interferes with BDNF-induced TrkB-mediated signal transduction and protection of cortical neurons from apoptosis evoked by deprivation from trophic support [Tong L., Balazs R., Soiampornkul R., Thangnipon W., Cotman C.W., 2007. Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction. Neurobiol. Aging]. Here we investigated whether the effect of the cytokine on neurotrophin signaling is more general. The influence of IL-1β on NT-3 signaling was therefore studied under conditions when NT-3 primarily activated the TrkC receptor. The cytokine reduced NT-3-induced activation of MAPK/ERK and Akt, but did not interfere with Trk receptor autophosphorylation. IL-1β reduced tyrosine phosphorylation of the docking proteins, IRS-1 and Shc, which convey receptor activation to the downstream protein kinase cascades. These are the steps that are also inhibited by IL-1β in BDNF-induced signal transduction. The functional consequences of the effect of IL-1β on NT-3 signaling were severe, as NT-3 protection of the trophic support-deprived cortical neurons was abrogated. In view of the role in the maintenance and plasticity of neurons of ERK, Akt and CREB, which are activated by neurotrophins, elevated IL-1β levels in the brain in Alzheimer's disease and other neurodegenerative diseases might contribute to the decline in cognitive functions before the pathological signs of the disease develop.

Influence of IL-1β and TNF-α on vimiten expression in cultured human retinal pigment epithelial cells

目的 观察IL-1β和TNF-α对培养的人视网膜色素上皮(RPE)细胞波形蛋白表达的影响.方法采用免疫组织化学和彩色图像分析技术检测IL-1β和/或TNF-α(20 ng/mL)对RPE细胞波形蛋白表达的影响.结果波形蛋白表达的灰度值分别为:IL-1β+TNF-α处理组76.9±8.1,IL-1β处理组78.4±8.1,TNF-α处理组90.2±6.7.与对照组110.2±10.7比较均有显著性差异(P＜0.01).结论IL-1β和/或TNF-α可上调波形蛋白的表达,在增生性玻璃体视网膜病变(PVR)中可能参与RPE细胞增殖过程中中间丝的改变。

Cytokine Sensitivity of Langerhans' Islets of Diabetes-prone BB/OK Rats under Hypoglycemic Conditions

Islets of Langerhans isolated from diabetes-prone BB/OK rats were exposed to interleukin-1β (IL-1β) or to a combination of tumor necrosis factor-α (TNF-α) plus interferon-γ (IFN-γ) under hypoglycemia at glucose concentrations of 2.2 and 3.2 mmol/l or in the presence of stimulatory conditions at 6.0 and 11 mmol/l glucose. For estimating cytokine effects the islets were functionally assayed by measurement of glucose stimulated insulin secretion. Pancreatic islets exposed for 24 h to IL-1β at a glucose concentration of 6.0 mmol/l exhibited a reduced insulin secretion following a 48 h recovery period compared to islets which were cytokine treated at 2.2 or 3.2 mmol/l glucose, respectively. Islets pre-exposed for 24 h to TNF-α plus IFN-γ at 2.2, 3.2 or 6.0 mmol/l glucose displayed no alterations of insulin secretion following a 48 h regeneration. A temporary (3 h) influence of IL-1β under hyperglycemic conditions at 11 mmol/l glucose caused a reduction of the subsequent insulin secretion of Langerhans' islets prior incubated for 24 h at 6.0 mmol/l glucose without cytokines, but not of islets precultured at 2.2 mmol/l glucose. In contrast, a 3 h treatment with TNF-α plus IFN-γ at 11 mmol/l glucose did not affect insulin secretion of islets prior held at 6.0 mmol/l glucose, whereas a transient exposure for 6 h to IL-1β as well as TNF-α plus IFN-γ under similar conditions diminished insulin secretion of islets preincubated at 2.2 or 6.0 mmol/l glucose. In conclusion, hypoglycemia reduces the sensitivity of BB/OK rat islets to IL-1β, whereas a slight elevation of glucose concentration to 6.0 mmol/l increases again their vulnerability. TNF-α plus IFN-γ at concentrations capable to decrease insulin secretion of islets during hyperglycemia do not affect the insulin output in a range between 2.2 and 6.0 mmol/l glucose. During glucose stimulation at 11 mmol/l islets' insulin secretory machinery is protected from IL-1β as well as TNF-α plus IFN-γ for 3 h by a preceding 24 h hypoglycemia, but its vulnerability is restored within additional 3 h.

Molecular mechanism underlying neurotrophic effects of BDNF on CNS neurons

It was previously observed that IL-1β interferes with BDNF-induced TrkB-mediated signal transduction and protection of cortical neurons from apoptosis evoked by deprivation from trophic support [Tong L., Balazs R., Soiampornkul R., Thangnipon W., Cotman C.W., 2007. Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction. Neurobiol. Aging]. Here we investigated whether the effect of the cytokine on neurotrophin signaling is more general. The influence of IL-1β on NT-3 signaling was therefore studied under conditions when NT-3 primarily activated the TrkC receptor. The cytokine reduced NT-3-induced activation of MAPK/ERK and Akt, but did not interfere with Trk receptor autophosphorylation. IL-1β reduced tyrosine phosphorylation of the docking proteins, IRS-1 and Shc, which convey receptor activation to the downstream protein kinase cascades. These are the steps that are also inhibited by IL-1β in BDNF-induced signal transduction. The functional consequences of the effect of IL-1β on NT-3 signaling were severe, as NT-3 protection of the trophic support-deprived cortical neurons was abrogated. In view of the role in the maintenance and plasticity of neurons of ERK, Akt and CREB, which are activated by neurotrophins, elevated IL-1β levels in the brain in Alzheimer's disease and other neurodegenerative diseases might contribute to the decline in cognitive functions before the pathological signs of the disease develop.

Stimulation of Langerhans cell migration in mice by tumour necrosis factor alpha and interleukin 1 beta.

Following contact sensitization or other forms of cutaneous trauma epidermal Langerhans cells (LC) are stimulated to migrate from the skin and to travel, via afferent lymphatics, to draining lymph nodes.1 We have demonstrated previously that tumour necrosis factor α (TNF-α), a keratinocyte-derived epidermal cytokine, provides one stimulus for LC migration.2 It has been shown that intradermal injection of mice with homologous recombinant TNF-α induces a rapid reduction in the frequency of epidermal LC local to the site of exposure and results, somewhat later, in the accumulation of dendritic cells (DC) in draining lymph nodes.3,4 Systemic (intraperitoneal) treatment of mice with a neutralizing anti-TNF-α antibody prior to topical sensitization with oxazolone, a potent contact allergen, was found to inhibit almost completely the accumulation of DC in draining nodes normally provoked by exposure to this chemical. Such treatment was found also to suppress the development of contact sensitization.5 In the present investigations we have examined whether another epidermal cytokine interleukin 1β (IL-1β), a product of LC, also plays a role in LC migration. Attention has focused on IL-lβ for three reasons. First, it has been shown that the development of contact hypersensitivity is compromised in 1L-1s gene deletion transgenics,6 or in mice that have been treated with an anti-IL-1β antibody.7 Second, there is evidence suggesting that IL-1β, a cytokine which is upregulated very rapidly following contact sensitization8, is able to provoke the increased expression of TNF-α by keratinocytes.7 Third, it has been claimed on the basis of experiments performed with human skin explants that IL-1β may affect LC migration in vitro.9 We here describe investigations in which the influence of IL-1β and TNF-α on LC migration and DC accumulation were examined.