Plasma Levels Of TNF-alpha Research Articles

Comparison of the effects of short-term hypolipidaemic treatment on plasma adipokine levels in men and women with isolated hypercholesterolaemia.

Hypolipidaemic agents were found to affect plasma adipokine levels, but no previous study has investigated whether this effect is sex-dependent. We retrospectively analysed 61 patients participating in our previous studies, who because of isolated hypercholesterolaemia were treated with simvastatin (40 mg daily), ezetimibe (10 mg daily) or simvastatin (40 mg daily) plus ezetimibe (10 mg daily). Plasma levels of leptin, adiponectin, visfatin, tumour necrosis factor-alpha (TNF-alpha), free fatty acids (FFA), and high-sensitivity C-reactive protein (hsCRP) were assessed separately for men and women before and after 30 days of treatment. At baseline, plasma levels of adiponectin and leptin were lower, while plasma levels of TNF-alpha were higher in men than in women. Administration of simvastatin and statin/ezetimibe combination for 30 days reduced plasma levels of hsCRP, FFA, leptin, visfatin, and TNF-alpha but increased plasma levels of adiponectin, while the effect of ezetimibe was much more limited. The effect of simvastatin and ezetimibe, administered alone or in combination, on plasma hsCRP, FFA, leptin, adiponectin, visfatin, and TNF-alpha did not differ between men and women. Irrespectively of sex, the changes in plasma adipokines and systemic-anti-inflammatory effects were more expressed in simvastatin - than in ezetimibe-treated patients and were strongest when both these agents were administered together. Our results show that sex differences do not determine the effect of hypolipidaemic agents on adipose tissue and low-grade inflammation.

Abstract 513: Evaluation of Proinflammatory Effects of Low Dose Angiotensin II Infusion in Intact Female Mice and Adiponectin Deficient Mice

Circulating vasoactive peptide Angiotensin II (ANGII) has a well-known role in the development of hypertension and other cardiovascular diseases. In addition it has significant proinflammatory actions in the vascular wall inducing the production of reactive oxygen species, inflammatory cytokines and adhesion molecules. It has been previously shown that estrogen in female mice protects against ANGII mediated hypertension and against proinflammatory effects. It is not clear if the protective effects of estrogen extend to adiponectin deficient mice. Adiponectin is one of the few peptides secreted by fat to have anti-inflammatory properties. The present study evaluates the effect of chronic ANGII infusion on expression of cytokines in female C57BL/6J and adiponectin deficient mice (adipo-/-). Female mice (24- 28wks), were implanted with osmotic pump containing either ANG II (800 ng/Kg /min) or saline. Blood samples and tissue were collected at the end of 14 days. Plasma levels of TNFalpha and IL6 were measured using enzyme linked immunoabsorbent assay. Renal tissue expression of the cytokines were quantified using real-time PCR (Eppendorf Realplex 4 mastercycler) and SYBR Green ROX mastermix. Plasma TNFα levels were similar in saline infused C57Bl/6J(11±1 pg/ml) and adiponectin deficient mice(10± 1 pg/ml). ANGII did not significantly increase TNFα in the control(14±3 pg/ml) or adipo-/- mice(13+1 pg/ml). Plasma IL6 levels were also not significantly different in the two groups. A microarray for mRNA expression of markers of endothelial activation and adhesion molecules was also performed in the renal tissue. Preliminary data show that TNFalpha mRNA expression levels were not increased by ANG II infusion and IL6 expression was undetectable. ANGII also did not alter E-Selectin,VCAM1, Collagen1a1 and eNOS expression. In conclusion, ANGII infusion did not result in a proinflammatory milieu in both female C57BL/6J and Adipo -/- mice.

Demonstration of ameliorative effect of lacosamide: in a rat model of sepsis-induced critical illness polyneuropathy

Objectives:Critical illness neuropathy (CIN) is a condition that may occur in diseases with severe systemic response, particularly in sepsis. The aim of this study is to investigate the potential anti-inflammatory and lipid-peroxidation inhibiting activities of lacosamide by measuring tumour necrotizing factor-alpha (TNF-alpha), C-reactive protein (CRP), malondialdehyde (MDA) and white blood cells (WBC) using electroneuromyography (ENMG) in rats with sepsis-induced critical illness neuropathy (SICIN).Methods:Cecal ligation and puncture (CLP) procedure was performed on 39 rats to induce a sepsis model. The study groups were designed as follows: Group 1: normal (nonoperative); Group 2: (sham-operated); Group 3: CLP (untreated group); Group 4: CLP and lacosamide 20 mg/kg; Group 5: CLP and lacosamide 40 mg/kg. TNF-alpha, C reactive protein, MDA and WBC levels was measured and compound muscle action potential (CMAP) distal latans, amplitudes were measured by using ENMG in rats with SICIN.Results:When untreated sepsis group was compared with both control and sham groups, CMAP amplitudes and latans were significantly lower (P < 000.1). When CLP, CLP+lacosamide 20 mg/kg and CLP+lacosamide 40 mg/kg groups were compared, plasma levels of TNF-alpha and MDA were significantly higher in the untreated CLP group (F = 12.74, P < 0.0001), (F = 19.43, P < 0.05). In the CLP+lacosamide 40 mg/kg group, CRP levels were significantly lower only compared to the CLP group (P < 0.001).Discussion:We have showed that lacosamide may have beneficial effects on early SICIN by its potential anti-inflammatory and lipid peroxidation inhibiting activities; however, further comprehensive studies are required to clarify these effects.

An experimental study of muscular injury repair in a mouse model of notexin-induced lesion with EPI® technique.

BackgroundThe mechanisms of muscle injury repair after EPI® technique, a treatment based on electrical stimulation, have not been described. This study determines whether EPI® therapy could improve muscle damage.MethodsTwenty-four rats were divided into a control group, Notexin group (7 and 14 days) and a Notexin + EPI group. To induce muscle injury, Notexin was injected in the quadriceps of the left extremity of rats. Pro-inflammatory interleukin 1-beta (IL-1beta) and tumoral necrosis factor-alpha (TNF-alpha) were determined by ELISA. The expression of receptor peroxisome gamma proliferator activator (PPAR-gamma), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-1 (VEGF-R1) were determined by western-blot.ResultsThe plasma levels of TNF-alpha and IL-1beta in Notexin-injured rats showed a significant increase compared with the control group. EPI® produced a return of TNF-alpha and IL-1beta values to control levels. PPAR-gamma expression diminished injured quadriceps muscle in rats. EPI® increased PPAR-gamma, VEGF and VEGF-R1 expressions. EPI® decreased plasma levels of pro-inflammatory TNF-alpha and IL-1beta and increased anti-inflammatory PPAR-gamma and proangiogenic factors as well as VEGF and VEGF-R1 expressions.ConclusionThe EPI® technique may affect inflammatory mediators in damaged muscle tissue and influences the new vascularization of the injured area. These results suggest that EPI® might represent a useful new therapy for the treatment of muscle injuries. Although our study in rats may represent a valid approach to evaluate EPI® treatment, studies designed to determine how the EPI® treatment may affect recovery of injury in humans are needed.

Periosteal microcirculatory reactions in a zoledronate-induced osteonecrosis model of the jaw in rats.

Nitrogen-containing bisphosphonates induce osteonecrosis mostly in the jaw and less frequently in other bones. Because of the crucial role of periosteal perfusion in bone repair, we investigated zoledronate-induced microcirculatory reactions in the mandibular periosteum in comparison with those in the tibia in a clinically relevant model of bisphosphonate-induced medication-related osteonecrosis of the jaw (MRONJ). Sprague-Dawley rats were treated with zoledronate (ZOL; 80 i.v. μg/kg/week over 8 weeks) or saline vehicle. The first two right mandibular molar teeth were extracted after 3 weeks. Various systemic and local (periosteal) microcirculatory inflammatory parameters were examined by intravital videomicroscopy after 9 weeks. Gingival healing disorders (∼100%) and MRONJ developed in 70% of ZOL-treated cases but not after saline (shown by micro-CT). ZOL induced significantly higher degrees of periosteal leukocyte rolling and adhesion in the mandibular postcapillary venules (at both extraction and intact sites) than at the tibia. Leukocyte NADPH-oxidase activity was reduced; leukocyte CD11b and plasma TNF-alpha levels were unchanged. Chronic ZOL treatment causes a distinct microcirculatory inflammatory reaction in the mandibular periosteum but not in the tibia. The local reaction in the absence of augmented systemic leukocyte inflammatory activity suggests that topically different, endothelium-specific changes may play a critical role in the pathogenesis of MRONJ. This model permits for the first time to explore the microvascular processes in the mandibular periosteum after chronic ZOL treatment. This approach may contribute to a better understanding of the pathomechanism and the development of strategies to counteract bisphosphonate-induced side effects.

173: Probiotics in a gnotobiotic piglet model of preterm infants

Mucosal surfaces of newborns are colonized by microbes in dependence on their delivery and nutrition. Are probiotics safety to Caesarean section derived immunocompromised preterm infants? Hysterectomy derived preterm germ-free piglets, either treated or non-treated with serum, were colonized with Lactobacillus rhamnosus (LGG) four hours after hysterectomy. Bacterial translocation of LGG, its protection against subsequent infection of the piglets with Salmonella Typhimurium, and induction of plasma and intestinal levels of inflammatory cytokines IL-1 beta, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha (xMAP), and HMGB1 (ELISA) were estimated. LGG did not translocate in one week old preterm piglets. It was found in mesenteric lymph nodes in piglets subsequently infected with S. Typhimurium only but it did not translocate to other organs (blood, liver, spleen, and lungs). Inflammatory cytokine values were not induced by LGG alone but they were dramatically increased in piglets infected with Salmonella . The piglets treated with mixed serum of adult sows showed reduced levels of inflammatory cytokines as in the intestine so in plasma. It is necessary to develop highly sensitive animal models to evaluate a safety of different probiotics for immunocompromised preterm infants. A high attention should be paid to a selection of suitable markers to evaluate possible risk of these probiotics. Inflammatory cytokines in the intestine/feces of preterm newborns should be a suitable candidates of such markers. This work was supported by Grants 13-14736S of the Czech Science Foundation , FR-TI4/504 of the Ministry of Industry and Trade of the Czech Republic and the Institutional Research Concept RVO: 61388971 of the Institute of Microbiology .

Cellular stress marker alteration and inflammatory response in pigs fed with an ochratoxin contaminated diet

Aim of this study was to characterize the effects of an ochratoxin A (181 ± 34 ng/g) contaminated diet on growth performances, blood parameters, systemic cytokine levels, cell stress markers and reactivity of immune system of weaned pigs.Growth performance was not affected by OTA consumption even if OTA levels increased in plasma, kidney and liver. OTA diminished the protein content in the serum and increased levels of TNF-alpha and IL-10 in plasma. HO-1 mRNA, indicative for cells stress, was decreased in the kidney but increased in the liver. Additionally, whole blood of the animals of the OTA-group showed a decreased capacity to respond with cytokine expression (mRNA and protein) to ex vivo challenge with LPS. In conclusion our findings indicate that chronic ingestion with OTA-contaminated feed, even at low level, is hazardous for the animal and virtually for human health, pig being an excellent model for human.

Respiratory mechanics and plasma levels of tumor necrosis factor alpha and interleukin 6 are affected by gas humidification during mechanical ventilation in dogs.

The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5), mechanical ventilation with dry oxygen dispensation, and Group II (n = 5), mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77). This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05). Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02). Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation.

Etanercept induces remission of polyarteritis nodosa: a case report.

Etanercept induces remission of polyarteritis nodosa: a case report.

What is the impact of SOCS3, IL-35 and IL17 in immune pathogenesis of recurrent pregnancy loss?

Objective: To investigate the plasma levels of interleukin-4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), IL-17, IL-35 and suppressor of cytokine signaling 3 (SOCS3) in the women with history of idiopathic recurrent pregnancy loss (RPL) and in the fertile controls.Methods: This study was conducted with 60 idiopathic RPL cases and 40 age-matched fertile controls. Mid-follicular plasma levels of IL-17, IFN-gamma, TNF-alpha, TGF-beta, IL-6, IL-4, IL-10, SOCS3 and IL-35 were assayed by an enzyme linked immunosorbent assay.Results: The mean age of RPL and control cases were 31.6 ± 0.6 and 32.1 ± 0.7 years, respectively. While plasma IL-35 and SOCS3 levels of RPL group were significantly lower than that of the control group; IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, IL-17 and TGF-beta levels of RPL group were significantly higher than that of the control group. The comparison of cytokine ratios between RPL and control groups indicated significantly high TNF-alpha/IL-10, TNF-alpha/IL-4, IFN-gamma/IL-10, IFN-gamma/IL-6 and IFN-gamma/IL-4 ratios in the RPL group. IL-35/IL-17 ratio was significantly low in the RPL group compared to that in the control group. Overstimulation of TNF-alpha presented moderate influence on recurrent miscarriage risk.Conclusion: Decreased SOCS3 and IL-35 plasma levels and increased Th1/Th2 cytokine ratios in RPL cases pointed out the supression of anti-inflammatory process and this supression might play an important role in the pathogenesis of idiopathic RPL.

Abstract 128: Angiotensin II Evoked Increases in Blood Pressure and Inflammatory Mediators in Adiponectin-Deficient Mice

Chronic low grade inflammation is considered a predisposing factor for vascular dysfunction and subsequent elevation of blood pressures. Adipose tissue is a well-known source of mediators that are proinflammatory. Adiponectin (APN) is one of the few proteins secreted by the adipose tissue that is known to have anti-inflammatory properties. APN deficiency has been shown to result in significant increases in the plasma levels of inflammatory mediators when provided with an appropriate stimulus. Our research question is does a proinflammatory milieu accelerate or potentiate the development of hypertension? Male wild type C57Bl/6J and adiponectin deficient (adipo-/-) mice (24-28 wks, 28-30g) were implanted with radiotelemeters (TA11PA-C10, DSI) for chronic measurement of blood pressures. The mice were allowed to recover from surgery and baseline blood pressures recorded for 7-10 days. These mice were then implanted subcutaneously with osmotic pumps containing Angiotensin II (ANGII, 800ng/kg/min) and blood pressures were recorded for another 14 days. Baseline blood pressures in the adiponectin deficient mice (105±2 mmHg, n=3) were significantly lower than that of wild type C57BL/6J mice (116±6, n=3). After 14 days, ANGII infusion increased the blood pressures to similar levels in adiponectin deficient( 144±10 mmHg) and the wild type mice (138±7 mmHg). In a separate group of mice, the effects of chronic ANGII infusion on plasma TNFalpha levels were evaluated using ELISA. After 14 days of infusion, plasma TNFalpha levels were similar in adiponectin deficient (5.30±0.97 pg/ml,n=3) and wild type (4.94±0.84 pg/ml, n=6) mice. The data suggest that adiponectin deficient mice were more susceptible to the prohypertensive effects of ANGII and the increases in blood pressures were not associated with significant differences in circulating inflammatory mediators such as TNFalpha.

P101 Comparative study with hydrogen sulfide (H2S)-releasing derivative of naproxen ATB-346, naproxen and cyclooxygenase (COX)-2 inhibitor in the mechanisms of gastric mucosa injury induced by stress

Naproxen belongs to commonly used NSAIDs associated with less cardiovascular toxicity than selective COX-2 inhibitors and other NSAIDs but its use is limited due to serious gastrointestinal (GI)-tract adverse effects. Novel H2S-releasing derivative of naproxen (ATB-346) was shown to inhibit COX-1 and prostaglandins (PGs) generation without causing mucosal damage unlike parent drug but whether ATB-346 can affect stress-induced gastric damage remains unknown. We compared ATB-346 vs naproxen and celecoxib and determined the role of reactive oxygen species and cytokines in the action of these NSAIDs against water immersion restraint stress (WRS)-induced gastric lesions in rats. WRS exposed animals were pretreated with (1) naproxen, (2) ATB-346 (0.5–40 m/kg i.g.), and (3) celecoxib (10 mg/kg i.g.) with or without ODQ (5 mg/kg i.p.), selective guanylate cyclase inhibitor or BCA (10 mg/kg i.p.), the inhibitor of H2S-synthesizing enzyme CSE. The number of gastric lesions was assessed by planimetry, the gastric blood flow (GBF) by H2-gas clearance technique, the malonyldialdehyde (MDA) concentration, MPO and PGE2 generation, the plasma level of IL-1beta and TNF-alpha and the expression of SOD and glutathione peroxidase (GPx) were determined by ELISA and RT-PCR. Pretreatment with ATB-346 dose-dependently reduced WRS-induced gastric lesions; the dose inhibiting these lesions by 50% being 29 mg/kg, caused significant rise in GBF and fall in MPO and MDA content. These effects of ATB-346 were reversed by cotreatment with ODQ but not BCA (p

Effect of chronic Angiotensin II infusion on plasma TNFalpha and IL 6 levels in adiponectin deficient mice (LB687)

Chronic low grade inflammation plays an integral part in the development of many types of cardiovascular diseases. Adipose tissue is a well known source of many proinflammatory mediators. Adiponectin (APN) is one of the few proteins secreted by the adipose tissue that is known to have anti‐inflammatory properties. Our research goal is to understand if APN deficiency contributes to a proinflammatory milieu especially when provided with an appropriate stimulus. Angiotensin II (ANGII) is a well known prohypertensive agent. Recently, ANGII has emerged as a growth factor and stimulator of proinflammatory cytokine expression in cardiovascular &amp;amp; renal tissue. The present study evaluates the effect of chronic Angiotensin II infusion on plasma TNFAlpha and IL 6 levels. Briefly, male C57BL/6J mice and Adiponectin deficient mice (adipo ‐/‐) were implanted with osmotic pumps containing Angiotensin II (ANGII, 800ng/Kg body weight/min) or Saline. Plasma levels of TNFalpha and IL6 were measured using enzyme linked immunoabsorbent assay (ELISA) kits. After two weeks of chronic infusion of ANGII, plasma TNFalpha levels in adiponectin deficient mice (n=6, 11.85±1.54 pg/ml) were not significantly different from the control C57Bl/6J mice (n=6, 9.88±1.17pg/ml). Plasma IL6 levels were also not significantly different in the two groups. In conclusion, adiponectin deficiency did not result in a proinflammatory milieu in the circulation even in the presence of a inflammatory stimulus such as ANGII.

Early life stress and tumor necrosis factor superfamily in crack cocaine withdrawal

BackgroundBoth early life stress (ELS) and substance abuse, especially cocaine, have robust effects on the inflammatory system. Considering the role of the tumor necrosis factor system in inflammatory signaling and its association with ELS, the aim of the study was to compare plasma levels of TNF-alpha, its soluble receptors and ligands during early abstinence of crack cocaine. MethodsThis study included 24 crack cocaine-dependent women with (CRACK-ELS) and 20 without (CRACK) a history of ELS. A healthy control group (HC), containing 25 participants, was included to provide reference values. The Childhood Trauma Questionnaire (CTQ) retrospectively assessed childhood maltreatment history of patients. Plasma levels of TNF-alpha, TNF-related weak inducer of apoptosis (TWEAK), TNF-related apoptosis-inducing ligand (TRAIL), soluble receptors TNFRI (sTNFRI) and TNFRII (sTNFRII) were assessed on the 18th day of treatment. ResultsThe CRACK-ELS group had higher TNF-alpha and lower TWEAK levels compared to the CRACK and HC groups. sTNFRII was increased, but only in comparison with the crack cocaine group and the controls. TRAIL levels were slightly higher in the CRACK-ELS group, while no differences were found for sTNFRI levels. Also, TNF-alpha plasma level was positively predicted by abstinence severity and childhood maltreatment severity, and TWEAK was negatively predicted by childhood maltreatment severity. ConclusionsThis is the first study to evaluate the newly secreted tumor necrosis factor superfamily ligands, TWEAK and TRAIL, during crack cocaine abstinence, supporting the association between early life stress and peripheral pro-inflammatory levels.

Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-β levels in pregnant women with preeclampsia, and their relation with severity of disease

Objective: To research the hypothesis of preeclampsia (PE) is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses; we evaluated the maternal plasma levels of IFN-gamma, TNF-alpha, TGF-beta, IL-4, IL-6, IL-10, IL-17, IL-35 and SOCS3 in preeclamptic and healthy pregnants.Methods: This study was conducted with 40 preeclamptic (study group) and 40 normotensive pregnant (control) women in third trimester when they were admitted to the labor and delivery unit. The extracted maternal plasma samples were assayed by an enzyme-linked immunosorbent assay. Statistical analysis was performed by SPSS 16.0 version.Results: While IFN-gamma and TGF-beta levels of preeclamptic women were significantly higher (p < 0.01), IL-35 and IL-17 levels of preeclamptic women were significantly lower (p < 0.01) than those of controls. The ratios of IFN-gamma/IL-10, IFN-gamma/IL-6, IFN-gamma/IL-4 were significantly high and ratio of IL-35/IL-17 was significantly low in the PE group compared to those in the control group. Maternal plasma SOCS3 levels showed negative correlation with blood pressure and proteinuria severity, but none of the cytokines showed influence on blood pressure and proteinuria after adjusting for maternal and gestational age.Conclusions: Increased IFN-gamma/TGF-beta production and reduced IL-35/IL-17/SOCS3 production in preeclamptic women may lead to less cytokine inhibitory activity in PE, which may account for the increased proteinuria and blood pressure in PE.

Plasma IL-6 levels correlate with clinical and ultrasound measures of arthritis in patients with systemic lupus erythematosus

The objective of this paper is to elucidate the role of specific cytokines in lupus (SLE) arthritis. Fifty SLE and 40 RA patients had an ultrasound (US) scan of their hand as per standardized protocols. US scores were expressed per joint and as a total 'US activity' score, (sum of power Doppler (PD) and grey-scale synovial hypertrophy scores in all joints) and a total erosion score. SLE disease activity was assessed (BILAG and SELENA-SLEDAI). Plasma levels of IL-6, TNF-alpha and BLyS were measured using sandwich ELISA kits (Quantikine kits, R & D). On the basis of the US results SLE patients were divided into three groups: erosive arthritis (n = 20), non-erosive arthritis (n = 18) and those with a normal US scan (n = 12). Across the SLE groups plasma IL-6 levels correlated with CRP (p < 0.001), hand deformity scores (p = 0.005), BILAG musculoskeletal score (p = 0.009), wrist PD score (p = 0.01), the presence of tenosynovitis (p = 0.008) and total US activity score (p < 0.001) (which remained constant when corrected for total BILAG score). Neither TNF-alpha nor BLyS levels correlated with US or clinical measures of lupus arthritis; however, TNF-alpha correlated with total BILAG score (p < 0.001). This is the first study to examine levels of specific cytokines in a cohort of SLE patients stratified in terms of joint disease by US, where the most significant finding is that IL-6 levels correlated both with clinical and US measures of arthritis disease activity.

Surveillance of Intra-Abdominal Pressure and Intestinal Barrier Function in a Rat Model of Acute Necrotizing Pancreatitis and Its Potential Early Therapeutic Window

ObjectivesTo monitor intra-abdominal pressure (IAP) and intestinal barrier function in a rat model of acute necrotizing pancreatitis (ANP) to elucidate a potential relevant therapeutic window.MethodsSprague-Dawley rats were randomly divided into experimental or control groups. The ANP group (n = 40) was injected with 4.5% sodium taurocholate into the pancreatic duct to induce ANP. The controls received only abdominal opening surgery (sham-operated, SO; n = 40) or no treatment or surgery (baseline; 0 h, n = 20). The SO and ANP groups were then randomly subdivided into 3, 6, 12 and 24 h groups (n = 10 each). IAP was measured at each time point and the rats were sacrificed to measure the weight of accumulated ascites fluid and the amylase, endogenous creatinine (Cr), total bilirubin (TB), tumor necrosis factor- alpha (TNF-alpha), diamine oxidase (DAO), and D-lactate. Mortality and the development of pathological changes in the pancreas and intestines were also monitored.ResultsIAP showed a continuous upward trend in the ANP group, with values 2 to 3 times higher than those in the SO group at the corresponding time points and the rising rate was peaking at 6 h. The levels of plasma amylase, TNF-alpha, Cr, TB, DAO, and D-lactate also gradually increased in the ANP group over time and were significantly higher than in the SO group at 3, 6, 12 and 24 h (all P<0.05). Moreover, the rising rate of TNF-alpha, DAO, and D-lactate also peaked at 6 h.ConclusionsThe ANP-induced changes in IAP, inflammatory factors and intestinal barrier that we observed in the rat model were especially obvious at 6 h post-induction, suggesting an early therapeutic window for the treatment of ANP in humans.

THU0314 Plasma IL-6 Levels Correlate with Ultrasound Measures of Disease Activity in Lupus Arthritis

BackgroundThe role of specific cytokines in lupus arthritis has not been elucidated1. This is in stark contrast to rheumatoid arthritis (RA) where an abundance of research has culminated in an...

Infant immune activation, HIV susceptibility and ochratoxin A exposure in Khayelitsha, South Africa (P6159)

Abstract In Khayelitsha, South Africa, 25% of new mothers are HIV-infected, and despite HIV acquisition through breast milk, WHO guidelines recommend breastfeeding to reduce infant mortality. One unexplained observation is that mixed fed infants (breast milk with formula/cereals) have up to an 11 fold increased risk of HIV acquisition. We hypothesized that this increase in HIV susceptibility is due to higher immune activation in response to non-breast milk foods. In fact, using non-invasive oral mucosa sampling, we observed increased CD4+ cells in mixed fed infants by flow cytometry. One immunomodulatory factor that may induce this immune activation in mixed fed infants is the common food contaminant Ochratoxin A (OTA). We measured OTA levels in plasma samples from infants in Khayelitsha, and found that at 2 weeks of age all infants had low OTA levels. However, at 6 weeks of age, OTA levels increased by 2 fold only in non-breastfed infants. Additionally, OTA plasma levels positively correlated with plasma levels of CXCL10 and TNF-alpha and negatively with IFN-alpha. Together, these data show that: 1. mixed fed infants have increased mucosal HIV target cells, 2. infant foods in Khayelitsha are contaminated with OTA, and 3. OTA exposure correlates with increased inflammatory and decreased antiviral activity in infant plasma. These findings suggest a mechanism for increased HIV susceptibility in mixed-fed infants and a role for food contaminants in infant HIV susceptibility.

Therapeutic Effects of the Superoxide Dismutase Mimetic Compound Me2DO2A on Experimental Articular Pain in Rats

Superoxide anion (O2 •−) is overproduced in joint inflammation, rheumatoid arthritis, and osteoarthritis. Increased O2 •− production leads to tissue damage, articular degeneration, and pain. In these conditions, the physiological defense against O2 •−, superoxide dismutases (SOD) are decreased. The MnII complex MnL4 is a potent SOD mimetic, and in this study it was tested in inflammatory and osteoarticular rat pain models. In vivo protocols were approved by the animal Ethical Committee of the University of Florence. Pain was measured by paw pressure and hind limb weight bearing alterations tests. MnL4 (15 mg kg−1) acutely administered, significantly reduced pain induced by carrageenan, complete Freund's adjuvant (CFA), and sodium monoiodoacetate (MIA). In CFA and MIA protocols, it ameliorated the alteration of postural equilibrium. When administered by osmotic pump in the MIA osteoarthritis, MnL4 reduced pain, articular derangement, plasma TNF alpha levels, and protein carbonylation. The scaffold ring was ineffective. MnL4 (10−7 M) prevented the lipid peroxidation of isolated human chondrocytes when O2 •− was produced by RAW 264.7. MnL4 behaves as a potent pain reliever in acute inflammatory and chronic articular pain, being its efficacy related to antioxidant property. Therefore MnL4 appears as a novel protective compound potentially suitable for the treatment of joint diseases.