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PubMed2006

Inflammation in preterm and term labour and delivery.

Inflammation has been implicated in the mechanisms responsible for preterm and term parturition, as well as fetal injury. Out of all of the suspected causes of preterm labour and delivery, infection and/or inflammation is the only pathological process for which both a firm causal link with preterm birth has been established and a molecular pathophysiology defined. Inflammation has also been implicated in the mechanism of spontaneous parturition at term. Most cases of histopathological inflammation and histological chorioamnionitis, both in preterm and term labour, are sub-clinical in nature. The isolation of bacteria in the amniotic fluid, known as microbial invasion of the amniotic cavity, is a pathological finding; the frequency of which is dependent upon the clinical presentation and gestational age. There is a window of time during which it may be possible to detect a 'molecular signature of inflammation' by analysis of the transcriptome before histological evidence is observed. This article reviews the role of inflammation in preterm and term parturition. It is possible that modulation of inflammation using anti-inflammatory cytokines, corticoids, antioxidants and/or other factors may complement antibiotic therapy and limit fetal injury.

Adrenal Cortex Hormones↗
PubMed2005

Relationship between chronic inflammation and cardiovascular risk factors in children on maintenance hemodialysis.

Cardiovascular disease is one of the most important causes of morbidity and mortality in children with end-stage renal failure. Chronic inflammation and malnutrition have been suggested to be risk factors for cardiovascular disease. However, to date, biomarkers of inflammation have not been well studied in children. The aim of this study was to investigate the relation between chronic inflammation and cardiovascular risk factors in children on hemodialysis therapy. Twenty-seven patients on hemodialysis (14 girls, 13 boys) of mean age 15.3 +/- 2.4 years and 20 healthy children (13 girls, 7 boys) of mean age 14.3 +/- 2.7 years were included the study. C-reactive protein (CRP), albumin, prealbumin, transferrin, ferritin, and fibrinogen were measured as the markers of inflammation. The levels of CRP, ferritin, and erythrocyte sedimentation rate among hemodialysis patients were significantly higher than those of control subjects (P < .001 for all). Albumin and transferrin levels were found to be lower than those of control group (P = .02 and P < .001, respectively). CRP levels were negatively correlated with albumin, prealbumin, apoprotein A1, HDL, and hemoglobin levels, and positively correlated with erythropoietin/Htc ratios. This study suggests that hemodialyzed children are exposed to chronic inflammation. In addition, CRP may be an indicator of chronic inflammation related to cardiovascular risk factors, such as malnutrition, dyslipidemia, and anemia. In conclusion, we suggest that the risk of cardiovascular disease could be reduced by defining markers of chronic inflammation and malnutrition in hemodialyzed children and by taking necessary measures at an early stage.

Adolescent↗
PubMed2001

Role of nerves in asthmatic inflammation and potential influence of gastroesophageal reflux disease.

Inflammation of the lower airways is a defining characteristic of asthma. Microaspiration of refluxate may initiate an inflammatory response in the airways of patients with gastroesophageal reflux disease (GERD), thereby precipitating asthma. Airway nerves are likely to play a role in the pathogenesis of asthma and could potentially mediate airway inflammation initiated by GERD through axonal reflexes. Alternatively, refluxate may initiate airway reflexes from the esophagus that are markedly exaggerated by inflammation-induced enhancement of airway neuronal excitability. The characteristic features of inflammation in asthma are defined, and the potential role of nerves in inflammation is discussed. Mechanisms by which GERD may initiate airway inflammation or act synergistically with airway inflammation to produce asthma also are discussed.

Animals↗
PubMed2003

A new model for inflammation-induced preterm birth: the role of platelet-activating factor and Toll-like receptor-4.

Preterm birth is a leading cause of neonatal morbidity and mortality. Despite a growing body of evidence correlating inflammation with preterm birth, the signal transduction pathways responsible for the emptying of the uterus in the setting of intrauterine inflammation has not been elucidated. We now report a unique, reproducible mouse model of localized intrauterine inflammation. This model results in 100% preterm delivery with no maternal mortality. Using our model, we also show that platelet-activating factor is a crucial mediator of both inflammation-induced preterm birth and fetal demise. Using C3H/HeJ mice, we demonstrate that toll-like receptor-4 (TLR-4) plays a role in lipopolysaccharide-induced preterm birth but not in inflammation-induced fetal death. Immunohistochemistry studies demonstrate the presence of the platelet-activating factor receptor in both endometrial glands and smooth muscle in uterine tissues. Molecular studies demonstrate the differential expression of platelet-activating factor receptor and TLR-4 in uterine and cervical tissue throughout gestation. Quantitative polymerase chain reaction revealed an up-regulation of TLR-4 in the fundal region of the uterus in response to intrauterine inflammation. The use of this model will increase our understanding of the significant clinical problem of inflammation-induced preterm birth and will elucidate signal transduction pathways involved in an inflammatory state.

Animals↗
PubMed2003

Involvement of oxytocin in spinal antinociception in rats with inflammation.

The present study was conducted on rats with inflammation induced by subcutaneous injection of carrageenan into the left hindpaw. Intrathecal administration of oxytocin produced dose-dependent increases in the hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats with inflammation. The antinociceptive effect of oxytocin was blocked by intrathecal administration of atosiban, a selective oxytocin antagonist, indicating that oxytocin receptor mediates oxytocin-induced antinociception in the spinal cord. The oxytocin-induced antinociceptive effect was attenuated by intrathecal administration of the opioid antagonist naloxone, suggesting an involvement of the endogenous opioid system in oxytocin-induced antinociception in the spinal cord of rats with inflammation. Furthermore, the antinociceptive effect of oxytocin was attenuated by intrathecal injections of the mu-receptor antagonist beta-funaltrexamine and the kappa-receptor antagonist nor-binaltorphimine, but not by the delta-receptor antagonist naltrindole, illustrating that mu- and kappa-receptors, but not delta-receptor, are involved in oxytocin-induced antinociception in the spinal cord of rats with inflammation. Moreover, intrathecal administration of atosiban alone induced a hyperalgesia in rats with inflammation, indicating that endogenous oxytocin is involved in the transmission and regulation of nociceptive information in the spinal cord of rats with inflammation. The present study showed that both exogenous and endogenous oxytocin displayed antinociception in the spinal cord in rats with inflammation, and mu- and kappa-receptors were involved in oxytocin-induced antinociception.

Analgesics↗
PubMed1999

The antinociceptive effect of the mu-opioid fentanyl is reduced in the presence of the alpha(2)-adrenergic antagonist idazoxan in inflammation.

Interactions between alpha(2)-adrenergic and mu-opioid systems play an important role in the modulation of hyperalgesic states. The antinociceptive effects of alpha(2)-adrenergic agonists and mu-opioids are potentiated when co-administered; however, attempts to induce cross reversal of the antinociceptive effects of alpha(2)-adrenergic and mu-opioid systems have produced contradictory results. We have studied the possible endogenous tonic control of the alpha(2)-adrenergic systems in the modulation of pain in inflammation, and the interactions between the two antinociceptive systems in rat spinal cord nociceptive reflexes activated by both natural and electrical stimulation. The facilitatory actions of the alpha(2)-adrenergic antagonist idazoxan were compared in control rats and in animals with carrageenan-induced paw inflammation. The antinociceptive effect of the mu-opioid fentanyl was tested alone and in the presence of idazoxan. In agreement with some previous observations, idazoxan i.v. produced no change in responses to natural and electrical stimulation in normal animals. In animals with inflammation, idazoxan only induced facilitation of responses evoked by noxious thermal stimulation but not by mechanical or electrical stimulation. Fentanyl reduced the responses to either stimuli with lower potency in the presence of idazoxan, but only in animals with inflammation. Its dose-response curve was shifted to the right between 1.8- and 3. 5-fold depending on the stimulus used. It is concluded that the increase of thermal responses by idazoxan in animals with inflammation is probably due to changes in the peripheral blood flow. Nevertheless, since an interaction with mu-opioids is clear in inflammation, endogenous alpha(2)-adrenergic systems play an important role in the modulation of the effectiveness of opioids during inflammation.

Adrenergic alpha-Antagonists↗
PubMed2001

Pharmacological action of melatonin in shock, inflammation and ischemia/reperfusion injury.

A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants (such as peroxynitrite) as mediators of inflammation, shock and ischemia/reperfusion injury. The aim of this review is to describe recent developments in the field of oxidative stress research. The first part of the review focuses on the roles of reactive oxygen species in shock, inflammation and ischemia/reperfusion injury. The second part of the review described the pharmacological action of melatonin in shock, ischemia/reperfusion, and inflammation. The role of reactive oxygen species: Immunohistochemical and biochemical evidence demonstrate the production of reactive oxygen species in shock, inflammation and ischemia/reperfusion injury. Reactive oxygen species can initiate a wide range of toxic oxidative reactions. These include the initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3 phosphate dehydrogenase, inhibition of membrane sodium/potassium ATP-ase activity, inactivation of membrane sodium channels, and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of shock, inflammation and ischemia and reperfusion. Treatment with melatonin has been shown to prevent in vivo the delayed vascular decompensation and the cellular energetic failure associated with shock, inflammation and ischemia/reperfusion injury. Reactive oxygen species (e.g., superoxide, peroxynitrite, hydroxyl radical and hydrogen peroxide) are all potential reactants capable of initiating DNA single-strand breakage, with subsequent activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. Recently, it has been demonstrated that melatonin inhibits the activation of poly (ADP-ribose) synthetase, and prevents the organ injury associated with shock, inflammation and ischemia and reperfusion.

Animals↗
PubMed1998

Linkage between inflammation and coagulation: an update on the molecular basis of the crosstalk.

Inflammation and coagulation cannot be considered as two separate processes, since there are several connecting points making them part of unique, defensive host response. The endothelium can be considered as the first link between inflammation and coagulation, since damaged endothelium during inflammation represents a surface where proteins involved in both coagulation and the development of inflammation are expressed. During inflammation, cytokines modulate the coagulation system by downregulating the expression of thrombomodulin and the activation of protein C pattern but, at the same time, they induce the expression of tissue factor, modifying, in this way, the balance between procoagulant and anticoagulant activities. At the same time, at the site of tissue injury, platelets become activated and release several mediators that modify tissue integrity. Thrombin, formed following activation of the coagulation cascade, is essential to promote haemostasis but also stimulates several cell functions, including chemotaxis and mitogenesis, which are responsible for the spreading of the lesion and the tissue repair process. Therefore, in the study of inflammation the involvement of the coagulation pathway has to be taken into account, since the interaction between coagulation and inflammation pathways is a critical issue.

Animals↗
PubMed1996

The anemia of inflammation. A common cause of childhood anemia.

Pediatricians should understand that the anemia of inflammation is second only to iron deficiency in overall incidence. When evaluating a child for mild to moderate anemia, one should always consider hemolytic anemia, both immune and congenital, and blood loss. Careful scrutiny of the peripheral blood smear is always helpful and can assist in minimizing expensive and unnecessary evaluations. When the anemia of inflammation is suggested by history or physical examination and the CBC reveals a normocytic, or possibly microcytic, mild to moderate anemia with a normal peripheral blood smear, it is prudent to not embark on an extensive evaluation for the anemia but instead wait for the inflammation to resolve. This may take as many as 3 months, depending on the degree of inflammation. Because the anemia resolves with subsiding inflammation, it is best to avoid treatment with iron or RBC transfusions. More studies need to be performed concerning the pathogenesis of the anemia of acute inflammation in children and the best course of treatment, if needed. The role of erythropoietin in the treatment of this form of anemia, though promising in some adult models of inflammation, awaits exploration in pediatric patients.

Adult↗
PubMed1999

Orofacial deep and cutaneous tissue inflammation differentially upregulates preprodynorphin mRNA in the trigeminal and paratrigeminal nuclei of the rat.

Preprodynorphin (PPD) and preproenkephalin (PPE) gene expression in a rat model of orofacial inflammation were examined in order to further characterize the neurochemical mechanisms underlying orofacial inflammation and hyperalgesia. Deep and cutaneous orofacial inflammation was produced by a unilateral injection of complete Freund's adjuvant (CFA) into the rat temporomandibular joint (TMJ) or perioral skin (PO), respectively. RNA blot analysis of the tissues including the spinal trigeminal complex revealed that the PPD mRNA level ipsilateral to TMJ inflammation was increased by 56.5+/-14.7% (n=4) when compared to the Naive group, and was significantly greater than the contralateral PPD mRNA level (p<0.05). The distribution of neurons that exhibited PPD mRNA after inflammation was localized by in situ hybridization (naive approximately 0). In TMJ-inflamed rats (n=6) PPD mRNA-positive neurons were found ipsilaterally in the medial portion of laminae I-II of the upper cervical dorsal horn (4.5+/-0.3), the dorsal portion of the subnucleus caudalis and caudal subnucleus interpolaris (5.2+/-0.3), and the paratrigeminal nucleus (6.4+/-1.2). A very localized induction of PPD mRNA was also identified in a group of neurons in the intermediate portion of the subnucleus caudalis (2.4+/-0.4) in PO-inflamed rats (n=6). The distribution of these PPD mRNA-positive neurons was somatotopically relevant to the site of injury. There were no significant changes in PPE mRNA expression in both TMJ- and PO-inflamed rats. These results indicate that TMJ inflammation resulted in a more intense and widespread increase in PPD mRNA expression when compared to PO inflammation. These changes may contribute to persistent central hyperexcitability and pain associated with temporomandibular disorders.

Animals↗
PubMed1996

Inflammation of the lungs, umbilical cord and placenta associated with meconium passage in utero. Review of 123 autopsied cases.

It is uncertain how often the passage of meconium in utero is a response to some event causing fetal distress as opposed to being simply the physiologic functioning of a maturing intestinal tract. The extent to which meconium may produce injury or inflammation in pulmonary and placental tissues after intrauterine exposure is also unclear. This study was a retrospective review of 123 cases, 79 stillborn and 44 liveborn less than one month of age, autopsied at The Johns Hopkins Hospital, and showing histologic evidence of intrauterine meconium exposure by aspirated meconium or meconium macrophages in placental tissues. Of 55 cases with pulmonary inflammation, 13 (24%) had fetal pneumonia, 5 (9%) had postnatal bronchopneumonia, and 37 (67%) had inflammation secondary to meconium aspiration. There was inflammation of the umbilical cord in 31 (41%) of the 75 cases with available slides, 11 (15%) had funisitis associated with chorioamnionitis and 18 (58%) were secondary to meconium exposure. There were 19 cases with focal injury of cord vessels from meconium, two of which had cord ulceration. Inflammation of the membranes and chorionic plate was present in 24 (33%) of the 72 cases where it could be assessed, and was due to chorioamnionitis in 11 (46%) and to meconium in 13 (54%). In general, meconium-related inflammations was much less severe in the membranes than in the cord. There were 67 (54%) cases with definite or probable evidence of fetal distress. In 38 (48%) stillborns no cause of fetal death in utero was identified and in 18 (41%) liveborns there was no known prenatal problem. The results support the concept that meconium passage in utero may occur either as a response to fetal distress or as a physiologic process. Inflammation in the lung and placental tissues, and vascular injury in the umbilical cord may arise secondary to in utero exposure to meconium.

Female↗
PubMed2003

[Inflammation and cystic fibrosis].

Lung inflammation plays a pivotal role in the pathogenesis of airway disease in cystic fibrosis (CF). Inflammation occurs very early and can be identified in very young infants. Inflammatory response is also more intense in CF than in non-CF airway inflammatory diseases. Among the different cell types involved in the airway inflammation, neutrophils are recognized to play a central role by releasing proinflammatory mediators, such as reactive oxygen species and proteolytic enzymes. Whether inflammation arises independently from infection remains debated. While infection was demonstrated to clearly amplify the inflammation, several studies argue for the possibility of an intrinsic inflammation. Finally, there is also evidence that the severity of pulmonary disease is linked to other genetic factors outside the CFTR gene locus, involved in host defence and inflammation.

Cystic Fibrosis↗
PubMed2003

Prevention of gut inflammation by Bifidobacterium in dextran sulfate-treated gnotobiotic mice associated with Bacteroides strains isolated from ulcerative colitis patients.

Indigenous Bacteroides strains are closely associated with the occurrence and exacerbation of ulcerative colitis (UC). In this study, we aimed to clarify the effect of Bifidobacterium strains, another major member of colonic bacteria, on the development of gut inflammation using gnotobiotic mouse models associated with Bacteroides strains isolated from UC patients. Dextran sulfate (DSS) administration induced inflammation in the large intestine, in particular of the cecum, in the gnotobiotic mice associated with three strains of Bacteroides vulgatus, judging from the myeloperoxidase activity, occult blood score, and IgG leakage into the intestinal contents. However, the severity of the inflammation was greatly reduced in the gnotobiotic mice associated with both B. vulgatus and Bifidobacterium strains. The severity of the cecal inflammation was well correlated with the concentration of succinic acid in the cecum. Bacteriologically, the density of B. vulgatus strain A (BV-A) greatly decreased and the predominant strain changed from BV-A to BV-B on additional association with Bifidobacterium strains. Among gnotobiotic mice associated with a single B. vulgatus strain, the severity of cecal inflammation in BV-A-associated mice was greater than that in BV-B-associated mice. Each Bifidobacterium strain produced compound(s) more effectively inhibiting the growth of BV-A than BV-B in in vitro culture. Taken together, these results suggest that the severity of DSS-induced gut inflammation is closely associated with a particular B. vulgatus strain, and that Bifidobacterium strains may repress exacerbation of intestinal inflammation through growth inhibition of the B. vulgatus strain.

Animals↗
PubMed2005

Coincidence planar imaging for dynamic [18F]FDG uptake in nude mice with tumors and inflammation: correlated with histopathology and micro-autoradiography.

The Institute of Nuclear Energy Research of Taiwan has developed a dynamic coincidence detection device for positron emitted radiotracer pharmacodynamic study in small mice models. In this study, we set up an experimental paradigm by determining [fluorine-18]-2-deoxy-2-fluoro-D-glucose ([18F]FDG) dynamic uptake in tumors and inflammations in nude mice as the foundation for future applications in therapy development. Histopathology and micro-autoradiography of these tumors and inflammations were obtained for confirmation. Dynamic coincidence planar images of six tumors and two inflammations in nude mice were acquired over 4 hours immediately after injection of 25.9 MBq of [18F]FDG into the right thigh of each animal. After image reconstruction, the lesion-to-background ratios were calculated in regions of interest over the lesion and contralateral thigh to determine the equilibrium status of the radiotracer. All mice were sacrificed for histopathologic examination and six of the mice were examined with micro-autoradiography. [18F]FDG uptake in tumors and inflammations both reached equilibrium about 3 hours after injection. At equilibrium, [18F]FDG uptake into tumors was two to four times higher than the background. Uptake into the 4-day and 8-day inflammations was 2.3 and 5.5 times higher than the background, respectively. Histopathology showed macrophage and neutrophil infiltration around the tumors and in the inflammations. Micro-autoradiography showed dense silver grains in the granulation tissue surrounding the tumors and inflammations. The preliminary results suggested that dynamic [18F]FDG coincidence planar imaging can help in determining the suitable time for static [18F]FDG imaging in nude mice models. The optimal time for static [18F]FDG positron emission tomography imaging was around 3 hours after injection. The paradigm for determining a dynamic [18F]FDG uptake pattern was demonstrated for future new therapeutic drug experimental use.

Animals↗
PubMed1994

Effects of acute and chronic inflammation on the pharmacokinetics of prednisolone in rats.

The effects of acute and chronic stages of carrageenan-induced air-pouch inflammation on the pharmacokinetics of prednisolone were studied in male Wistar rats. Chronic inflammation produced a significant increase in the area under the curve (AUC) of prednisolone compared to control animals (6594 +/- 2144 vs 3530 +/- 2164 micrograms.hr/L). The effect of acute inflammation was not significant (AUC = 4996 +/- 3813). Both acute and chronic inflammation also reduced the in vitro plasma protein binding of prednisolone, the reduction being much greater after chronic inflammation. The AUC of free prednisolone after chronic inflammation was 3141 micrograms.hr/L, compared to 1121 micrograms.hr/L in the control group and 1823 micrograms.hr/L after acute inflammation. The mean values of half-life and apparent volume of distribution at steady-state in each group were similar. These results indicate that prednisolone must be used with caution in the treatment of inflammatory diseases because of higher free concentrations of the steroid.

Acute Disease↗
PubMed2000

Oxidative stress and regulation of glutathione in lung inflammation.

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance, a major cause of cell damage. The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox-sensitive transcription factors such as nuclear factor-KB, and activator protein-1 (AP-1), which regulate the genes for pro-inflammatory mediators and protective antioxidant genes. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro-inflammatory processes in the lungs. Recent findings have suggested that GSH is important in immune modulation, remodelling of the extracellular matrix, apoptosis and mitochondrial respiration. The rate-limiting enzyme in GSH synthesis is gamma-glutamylcysteine synthetase (gamma-GCS). The human gamma-GCS heavy and light subunits are regulated by AP-1 and antioxidant response elements and are modulated by oxidants, phenolic antioxidants, growth factors, and inflammatory and anti-inflammatory agents in lung cells. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis and asthma. The imbalance and/or genetic variation in antioxidant gamma-GCS and pro-inflammatory versus antioxidant genes in response to oxidative stress and inflammation in some individuals may render them more susceptible to lung inflammation. Knowledge of the mechanisms of GSH regulation and balance between the release and expression of pro- and anti-inflammatory mediators could lead to the development of novel therapies based on the pharmacological manipulation of the production as well as gene transfer of this important antioxidant in lung inflammation and injury. This review describes the redox control and involvement of nuclear factor-kappaB and activator protein-1 in the regulation of cellular glutathione and gamma-glutamylcysteine synthetase under conditions of oxidative stress and inflammation, the role of glutathione in oxidant-mediated susceptibility/tolerance, gamma-glutamylcysteine synthetase genetic susceptibility and the potential therapeutic role of glutathione and its precursors in protecting against lung oxidant stress, inflammation and injury.

Cysteine↗
PubMed2005

Continuous, noninvasive monitoring of local microscopic inflammation using a genetically engineered cell-based biosensor.

Using an inflammation-responsive regulatory element as a molecular sensor, we established a cell-based biosensor for continuous, noninvasive monitoring of local microscopic inflammation in vivo. Glomerular mesangial cells were stably transfected with a marker gene encoding secreted alkaline phosphatase (SEAP) under the control of the kappaB enhancer elements. The established cells secreted SEAP in vitro in response to proinflammatory cytokines as well as to soluble factors produced by inflamed glomeruli. To examine feasibility of using the established cells for in vivo monitoring of local microscopic inflammation, the sensor cells were transferred selectively into rat glomeruli via the renal circulation. After induction of acute glomerulonephritis, the serum level of SEAP was increased transiently in cell-transferred nephritic rats. The kinetics of serum SEAP was closely correlated with the natural course of the inflammation, and the increase in SEAP was attenuated by suppression of inflammation using an immunosuppressive drug, cyclophosphamide. Neither cell-transferred normal rats nor nephritic rats without cell transfer exhibited increase in the serum level of SEAP. When the sensor cells were transferred extrarenally, elevation of serum SEAP was not observed in nephritic rats, confirming that the locally settled sensor cells responded only to local inflammation. These results suggested that, without invasive procedures like tissue biopsies, continuous monitoring of microscopic inflammation is feasible in vivo via locally created, cell-based biosensors.

Acute Disease↗
PubMed2006

Elevated tumour interleukin-1beta is associated with systemic inflammation: A marker of reduced survival in gastro-oesophageal cancer.

Systemic inflammation is associated with adverse prognosis cancer but its aetiology remains unclear. We investigated the expression of proinflammatory cytokines within normal mucosa from healthy controls and tumour tissue in cancer patients and related these levels with markers of systemic inflammation and with the presence of a tumour inflammatory infiltrate. Tissue was collected from 56 patients with gastro-oesophageal cancer and from 12 healthy controls. Tissue cytokine mRNA concentrations were measured by real-time PCR and tissue protein concentrations by cytometric bead array. The degree of chronic inflammatory cell infiltrate was recorded. Serum cytokine and acute phase protein concentrations (including C-reactive protein (CRP)) were measured by enzyme-linked immunosorbent assay. Proinflammatory cytokines were significantly overexpressed (interleukin (IL)-1beta, IL-6, IL-8 and tumour necrosis factor-alpha) both at mRNA and protein levels in the cancer specimens compared with mucosa from controls. Interleukin-1beta was expressed in greatest (10-100-fold) concentration and protein levels correlated significantly with systemic inflammation (CRP) (P = 0.05, r = 0.31). A chronic inflammatory infiltrate was observed in 75% of the cancer specimens and was associated with systemic inflammation (CRP: P = 0.01). However, the presence of chronic inflammation per se was not associated with altered cytokine expression within the tumour. Both a chronic inflammatory infiltrate and systemic inflammation (CRP) were associated with reduced survival (P = 0.05 and P = 0.03, respectively). Tumour chronic inflammatory infiltrate and tumour tissue IL-1beta overexpression are potential independent factors influencing systemic inflammation in oesophagogastric cancer patients.

Acute-Phase Proteins↗