interleukin-8 and Hypothermia

Deep hypothermia with low flow perfusion (DHLF) is a common cardiopulmonary bypass (CPB) technique. The associated lung ischemia/reperfusion injury is a major cause of postoperative morbidity and mortality in patients undergoing DHLP; we aimed to investigate the effects of nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) with continuous perfusion of pulmonary arteries (CPP) on DHLF-induced lung injury and the related molecular mechanisms. Twenty-four piglets were randomly divided into the DHLF (control), CPP (with DHLF), or CPP+PDTC (intravenous PDTC before CPP with DHLF) groups. Lung injury was evaluated by respiratory function measurement, lung immunohistochemistry, and serum levels of TNF, IL-8, IL-6, and NF-κB before CPB, at CPB completion, and at 1 h post-CPB. Western blot was used to detect NF-κB protein expression in lung tissues. After CPB, decreased parcial pressure of oxygen (PaO2) and increased parcial pressure of carbon dioxide (PaCO2) and serum levels of TNF, IL-8, IL-6, and NF-κB were observed in the DHLF group. Both CPP and CPP+PDTC groups showed better indices of lung function, decreased levels of TNF, IL-8, and IL-6, and less severe pulmonary edemas and injuries. PDTC with CPP further improved pulmonary function and mitigated pulmonary injury than did CPP alone. PDTC with CPP better attenuates DHLF-induced lung injury than does CPP alone.

Topics: Animals; Hypothermia; Interleukin-6; Interleukin-8; Lung Injury; NF-kappa B; Perfusion; Pulmonary Artery; Swine

Therapeutic hypothermia is a promising candidate for stroke treatment although its efficacy has not yet been demonstrated in patients. Changes in blood molecules could act as surrogate markers to evaluate the efficacy and safety of therapeutic cooling.. Blood samples from 54 patients included in the EuroHYP-1 study (27 treated with hypothermia, and 27 controls) were obtained at baseline, 24 ± 2 h, and 72 ± 4 h. The levels of a panel of 27 biomarkers, including matrix metalloproteinases and cardiac and inflammatory markers, were measured.. Metalloproteinase-3 (MMP-3), fatty-acid-binding protein (FABP), and interleukin-8 (IL-8) increased over time in relation to the hypothermia treatment. Statistically significant correlations between the minimum temperature achieved by each patient in the hypothermia group and the MMP-3 level measured at 72 h, FABP level measured at 24 h, and IL-8 levels measured at 24 and 72 h were found. No differential biomarker levels were observed in patients with poor or favorable outcomes according to modified Rankin Scale scores.. Although the exact roles of MMP3, FABP, and IL-8 in hypothermia-treated stroke patients are not known, further exploration is needed to confirm their roles in brain ischemia.

Topics: Biomarkers; Humans; Hypothermia; Hypothermia, Induced; Interleukin-8; Ischemic Stroke; Matrix Metalloproteinase 3; Stroke

Hypothermia with xenon gas has been used to reduce brain injury and disability rate after perinatal hypoxia-ischemia. We evaluated xenon gas therapy effects in an in vitro model with or without hypothermia on cultured human airway epithelial cells (Calu-3).. Calu-3 monolayers were grown at an air-liquid interface and exposed to one of the following conditions: 1) 21% FiO2 at 37°C (control); 2) 45% FiO2 and 50% xenon at 37°C; 3) 21% FiO2 and 50% xenon at 32°C; 4) 45% FiO2 and 50% xenon at 32°C for 24 hours. Transepithelial resistance (TER) measurements were performed and apical surface fluids were collected and assayed for total protein, IL-6, and IL-8. Three monolayers were used for immunofluorescence localization of zonula occludens-1 (ZO-1). The data were analyzed by one-way ANOVA.. TER decreased at 24 hours in all treatment groups. Xenon with hyperoxia and hypothermia resulted in greatest decrease in TER compared with other groups. Immunofluorescence localization of ZO-1 (XY) showed reduced density of ZO-1 rings and incomplete ring-like staining in the 45% FiO2- 50% xenon group at 32°C compared with other groups. Secretion of total protein was not different among groups. Secretion of IL-6 in 21% FiO2 with xenon group at 32°C was less than that of the control group. The secretion of IL-8 in 45% FiO2 with xenon at 32°C was greater than that of other groups.. Hyperoxia and hypothermia result in detrimental epithelial cell function and inflammation over 24-hour exposure. Xenon gas did not affect cell function or reduce inflammation.

Topics: Anesthetics, Inhalation; Cells, Cultured; Humans; Hyperoxia; Hypothermia; Hypoxia-Ischemia, Brain; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Respiratory Mucosa; Tight Junctions; Treatment Outcome; Xenon

Recent literature suggests hypothermia may protect against lung injury. We evaluated body temperature as a variable in lung inflammation due to oxygenation and mechanical ventilation following delivery of near-term lambs.. Twin fetuses were randomized prior to delivery at 140 d GA (term 150 d): unventilated controls, normothermic ventilated with room air, normothermic ventilated with 100% oxygen, low temperature ventilated (target 35 degrees C) with 100% oxygen, and high temperature (target 40 degrees C) with 100% oxygen. Lambs were intubated for gentle mechanical ventilation (tidal volume 7-8ml/kg). Temperature targeting was with radiant warmers and plastic wrap for normothermia, with heat lamps for hyperthermia, and with ice packs for hypothermia. Lambs were euthanized after 2h mechanical ventilation. Post-mortem, bronchoalveolar lavage fluid and lung tissue samples were evaluated for inflammatory responses by measuring inflammatory cell counts, protein, myeloperoxidase, protein carbonyl, and pro-inflammatory cytokine mRNA.. Target temperatures were achieved by 30min of age and tightly maintained for the 2h study. There were no differences in physiologic variables among groups except those directly resulting from study protocol-PaO2 from air vs. 100% oxygen and body temperature. Indicators of inflammation increased similarly in all ventilated groups compared to unventilated controls.. Moderate hyperthermia or hypothermia did not affect lung injury responses to the initiation of ventilation at birth in near-term lambs.

Topics: Animals; Body Temperature; Bronchoalveolar Lavage Fluid; Cell Count; Disease Models, Animal; Fetus; Humans; Hyperthermia, Induced; Hypothermia; Hypothermia, Induced; Infant, Newborn; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Lung; Random Allocation; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Sheep; Treatment Outcome; Twins

Hypothermia is a standard method for organ protection during cardiac surgery in children. However, the mechanisms of hypothermia-induced cell protection have not yet been clearly established. Therefore, the aim of our studies was to elucidate molecular effects of clinically relevant mild and deep hypothermia on endothelial cells. The endothelium plays a pivotal role in the interaction between blood cells and actively participates in complex inflammatory events. We isolated primary human umbilical vein endothelial cells (HUVEC) and investigated cell viability, proliferation and inflammatory characteristics after TNF-alpha stimulation under mild (32 degrees C) and deep (17 degrees C) hypothermia in comparison to normothermia (37 degrees C). As a protective mechanism of endothelial cells kept under hypothermic conditions we found a significant upregulation of the antiapoptotic protein Bcl-2, resulting in the same cell viability under hypothermic conditions. Unexpectedly we demonstrated significantly higher IL-6 release after 6h of mild hypothermia. In contrast, hypothermia diminished inflammatory chemokines such as IL-8, MCP-1 and COX-2 protein expression which could lead to reduced leukocyte recruitment under hypothermia. Underlying mechanisms of this downregulation were found to be reduced ERK 1/2 phosphorylation and incomplete IkappaB-alpha degradation resulting in reduced NFkappaB-dependent proinflammatory gene expression. The upregulation of Bcl-2 protein and the higher IL-6 release after 6h of mild hypothermia are new and interesting cellular mechanisms of hypothermia in endothelial cell biology. Both factors may play a major role as cell protective mechanisms in hypothermia.

Topics: Cell Proliferation; Cell Survival; Cells, Cultured; Chemokine CCL2; Cyclooxygenase 2; Endothelial Cells; Humans; Hypothermia; Inflammation; Interleukin-6; Interleukin-8; MAP Kinase Signaling System; Phosphorylation; Time Factors; Tumor Necrosis Factor-alpha

This study assessed whether hyperglycemia and lipopolysaccharide (LPS) decrease the depression effect of interleukin (IL) 8 production by hypothermia in endothelial cells.. Laboratory study in a university laboratory.. Human umbilical vein endothelial cells (HUVECs).. HUVECs were cultivated in various concentrations of glucose (5.5 or 16.5mM = 100 or 300mg/dl) with or without LPS stimulation for 5, 12, or 24h at either 30 degrees or 37 degrees C.. After culturing, IL-8 mRNA expressions and IL-8 levels were measured. At 37 degrees C, hyperglycemia significantly increased basal IL-8 mRNA at 12h and basal IL-8 at 24h. At 37 degrees C hyperglycemia significantly increased LPS-stimulated IL-8 mRNA at 12h and LPS-stimulated IL-8 at 12 and 24h. At 30 degrees C basal IL-8mRNA, basal IL-8, and LPS-stimulated IL-8 were significantly decreased by hypothermia, but these hypothermic effects were not observed in LPS-stimulated IL-8 mRNA. Furthermore even at 30 degrees C hyperglycemia significantly increased LPS-stimulated IL-8 mRNA at all time points and LPS stimulated IL-8 at 24h.. Hypothermia (30 degrees C) decreases the production of IL-8 in HUVECs but does not decrease the expression of IL-8 mRNA. When hypothermia is followed by hyperglycemia and LPS stimulation, such a combination may expose the patients to a high risk of secondary tissue damage during therapeutic hypothermia.

Topics: Endothelial Cells; Gene Expression; Humans; Hyperglycemia; Hypothermia; Interleukin-8; Lipopolysaccharides; Umbilical Veins

Hypothermia is often associated with compromised host defenses and infections. Deterioration of immune functions related to hypothermia have been investigated, but the involvement of cytokines in host defense mechanisms and in infection remains unclear. Therefore, we determined whether mild hypothermia affects the production of several types of cytokines in peripheral blood mononuclear cells (PBMCs), and the balance between pro-inflammatory and anti-inflammatory states.. PBMCs obtained from 12 healthy humans were cultured with phytohemagglutinin (PHA) in normothermic (37 degrees C: control) or hypothermic (33 degrees C) conditions for 24 h. The production levels of tumor necrosis factor (TNF)-alpha, the interleukins (ILs) IL-6, IL-8 and IL-10, and interferon (IFN)-gamma in the culture supernatants were measured by means of enzyme-linked immunosorbent assay (ELISA).. Under hypothermic conditions (33 degrees C), PHA-induced production of IL-10 and IFN-gamma in PBMCs was significantly lower, by 34% and 84%, respectively, when compared with controls, while production of TNF-alpha, IL-6 and IL-8 did not change. The magnitude of reduction of IL-10 in hypothermic conditions resulted in IL-10/pro-inflammatory cytokine ratios decreasing to approximately 30-45% of those of controls.. The present study clearly demonstrates that mild hypothermia (33 degrees C) inhibits IL-10 and IFN-gamma production in cultured PBMCs. The profound inhibition of IL-10 and the pro-inflammatory reaction-dominated state induced suggests that the host defense mechanism against secondary infection may be maintained rather than inhibited in hypothermia. Thus, the reduction of IL-10 could be an important characteristic of immune responses in mild hypothermia.

Topics: Adult; Female; Humans; Hypothermia; Interferon-gamma; Interleukin-10; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Tumor Necrosis Factor-alpha

We have demonstrated recently that therapeutic moderate hypothermia of 32-33 degrees C, induced by surface cooling under the administration of narcotics, sedatives and muscle relaxant, suppresses cytokine production after traumatic brain injury. We present here the first documented case report of augmented cytokine production in two accidental hypothermia patients, unconscious 84- (acute immersion) and 87- (non-immersion) year-old women, whose rectal temperatures were below 28 degrees C. The victims were artificially ventilated after sedation with midazolam and buprenorphine in accordance with our protocol. Rewarming at the rate of approximately 1 degrees C/h was done by blowing forced-air with appropriate fluid resuscitation. Plasma interleukin(IL)-6 and/or IL-8 levels were measured using ELISA in the patients. In both patients, plasma IL-6 levels on admission were already elevated and the cytokine levels further increased during and after the rewarming period. In the patient with the poorer prognosis, the plasma IL-8 level on admission was not elevated remarkably but after rewarming the level rose significantly. Augmented IL-6 production in accidental hypothermia was sustained for 6 days in the patient with the poorer prognosis but not in the subject with good recovery, who was treated with anti-thrombin III in the early phase. Since the mechanisms for developing accidental hypothermia were different, simple comparisons between the two cases should be limited. But, these findings may suggest a need for testing a hypothesis whether cytokine modulation could be a therapeutic approach worthy of consideration. The results presented here also suggest that in hypothermia, changes in cytokine release may vary depending on procedures such as the anesthetic drugs used, the duration of the therapy, or the rate of rewarming from hypothermia.

Topics: Aged; Aged, 80 and over; Biomarkers; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypothermia; Interleukin-6; Interleukin-8; Prognosis; Rewarming; Sensitivity and Specificity