Animals ; Cytokines ; physiology ; Humans ; Immune System ; drug effects ; physiology ; Melatonin ; pharmacology ; Opioid Peptides ; physiology ; Receptors, Melatonin ; physiology ; Stress, Physiological ; immunology ; T-Lymphocytes ; drug effects ; physiology

OBJECTIVETo investigate the effects of different anesthetic and analgesic protocols on the cellular immune function and stress hormone in patients undergoing lobectomy for esophagus cancer.

METHODSSixty ASA I or II patients undergoing lobectomy for esophagus cancer were randomly divided into two groups to receive postoperative general anesthesia and intravenous analgesia (group A, n=30) or intraoperative general anesthesia combined with thoracic epidural anesthesia with postoperative epidural analgesia (group B, n=30). The cervical venous blood samples were obtained from the patients at 30 min before anesthesia induction (T(0)), 2 h after skin incision (T(1)), and at 4 h (T(2)), 24 h (T(3)) and 48 h (T(4)) after the end of operation. The T-lymphocyte subsets (CD4(+) and CD8(+)) were analyzed by flow cytometry, serum concentrations of sIL-2R and IL-2 determined by ELISA, and the levels of growth hormone (GR), prolactin (PRL), IL-8 and cortisol (Cor) measured by radioimmunoassay. Visual analogue scale (VAS) was used for assessment of the postoperative analgesic effects.

RESULTSThe VAS scores were significantly lower in group B than in group A at T(2) and T(3) (P<0.05). The percentage of CD4(+) cells and the CD4(+)/CD8(+) ratio in the two groups began to decrease significantly at T(1) (P<0.05), reducing to the lowest level at T(2) in group B and at T(3) in group A. From T(1) to T(4), the percentage of CD4(+) in group B remained significantly higher than those in group A (P<0.05), and from T(3) to T(4), the CD4(+)/CD8(+) ratio in group B were significantly higher than those in group A (P<0.05). The IL-2 level in the two groups began to decrease significantly at T(1) (P<0.05), reaching the lowest level at T(2) in group A and at T(3) in group A. IL-2 level was significantly higher in group B than in group A from T(3) to T(4) (P<0.05). sIL-2R level in group A began to increase at T(1) and peaked at T(3), showing significant differences from the T(0) level, but the level showed no significant variations in group B compared with the T(0) level. From T(2) to T(4), sIL-2R level was significantly higher in group A than in group B (P<0.05). The levels of GH, PRL and Cor increased significantly, while IL-8 decreased in the two groups from T(1) to T(4) (P<0.05), but remained stable in group B.

CONCLUSIONGeneral anesthesia combined with thoracic epidural anesthesia may reduce the perioperative stress reaction and adverse effect on cellular immune function in patients undergoing lobectomy for esophagus cancer.

Adult ; Aged ; Analgesia, Epidural ; methods ; Anesthesia, Epidural ; methods ; Anesthesia, Intravenous ; methods ; Esophageal Neoplasms ; immunology ; surgery ; Female ; Humans ; Immunity, Cellular ; drug effects ; Male ; Middle Aged ; Pain, Postoperative ; drug therapy ; Postoperative Period ; Stress, Physiological ; drug effects ; T-Lymphocytes ; immunology

This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the alpha1-adrenergic receptor (alpha1-AR) and beta2-adrenergic receptor (beta2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of alpha1-AR and beta2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1beta, IL-6 and IL-8 were detected after pretreatment with the alpha1/beta2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, alpha1-AR and beta2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of alpha1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of alpha1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1beta, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an alpha1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.
Adrenergic alpha-1 Receptor Antagonists/*therapeutic use ; Animals ; Cells, Cultured ; Cytokines/immunology ; Fibroblasts/immunology/pathology ; Humans ; Lipopolysaccharides/administration & dosage/immunology ; Male ; Periodontal Ligament/cytology/immunology/pathology ; Periodontitis/*drug therapy/*etiology/immunology/pathology ; Phentolamine/*therapeutic use ; Rats ; Rats, Wistar ; Receptors, Adrenergic, alpha-1/analysis/*immunology ; Signal Transduction/drug effects ; *Stress, Physiological/drug effects ; Tyrosine 3-Monooxygenase/analysis/immunology

AIMTo determine whether 7-oxo-dehydroepiandrosterone (7-oxo-DHEA) can reverse the hypoimmunity in BALB/c mice exposed to chronic mild stress.

METHODSA chronic mild stress animal model was established by subjecting BALB/c mice to a stressful regimen arranged in an unpredicted manner for 4 consecutive weeks. Immunological function alternations under chronic mild stress were assessed by lymphocytes proliferative response to mitogens and NK cell lysis activity test.

RESULTSThe studies showed the correlation between the state of depression and abnormalities in the immune response, such as a decrease of T lymphocytes proliferative response to Con A and suppression of cytotoxic of NK cell. Meanwhile, significant decrease of T3 and T4 levels was also observed. When stressed mice were daily given 7-oxo-DHEA 15 mg.kg-1, lymphocyte proliferative response and the NK cell activity were significantly enhanced and the decreased levels of T3 and T4 were restored in the stressed mice.

CONCLUSION7-oxo-DHEA can improve the depressive symptoms and hypoimmunity of BALB/c mice induced by chronic mild stress as its parent DHEA.

Adjuvants, Immunologic ; pharmacology ; Animals ; Antidepressive Agents ; pharmacology ; Cell Division ; drug effects ; Chronic Disease ; Dehydroepiandrosterone ; analogs & derivatives ; pharmacology ; Killer Cells, Natural ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Stress, Physiological ; blood ; immunology ; T-Lymphocytes ; immunology ; pathology ; Thyroxine ; blood ; Triiodothyronine ; blood

Endoplasmic reticulum (ER) stress regulates a wide range of cellular responses including apoptosis, proliferation, inflammation, and differentiation in mammalian cells. In this study, we observed the role of 2-deoxy-D-glucose (2DG) on inflammation of chondrocytes. 2DG is well known as an inducer of ER stress, via inhibition of glycolysis and glycosylation. Treatment of 2DG in chondrocytes considerably induced ER stress in a dose- and time-dependent manner, which was demonstrated by a reduction of glucose regulated protein of 94 kDa (grp94), an ER stress-inducible protein, as determined by a Western blot analysis. In addition, induction of ER stress by 2DG led to the expression of COX-2 protein with an apparent molecular mass of 66-70kDa as compared with the normally expressed 72-74 kDa protein. The suppression of ER stress with salubrinal (Salub), a selective inhibitor of eif2-alpha dephosphorylation, successfully prevented grp94 induction and efficiently recovered 2DG-modified COX-2 molecular mass and COX-2 activity might be associated with COX-2 N-glycosylation. Also, treatment of 2DG increased phosphorylation of Src in chondrocytes. The inhibition of the Src signaling pathway with PP2 (Src tyrosine kinase inhibitor) suppressed grp94 expression and restored COX-2 expression, N-glycosylation, and PGE2 production, as determined by a Western blot analysis and PGE2 assay. Taken together, our results indicate that the ER stress induced by 2DG results in a decrease of the transcription level, the molecular mass, and the activity of COX-2 in rabbit articular chondrocytes via a Src kinase-dependent pathway.
Animals ; Cartilage, Articular/pathology ; Cells, Cultured ; Chondrocytes/drug effects/immunology/*metabolism/pathology ; Cyclooxygenase 2/genetics/*metabolism ; Deoxyglucose/*pharmacology ; Down-Regulation ; Endoplasmic Reticulum/drug effects/*metabolism/pathology ; Glycosylation/drug effects ; Inflammation ; Rabbits ; Signal Transduction/drug effects ; Stress, Physiological/drug effects/immunology ; src-Family Kinases/*metabolism