- Email: [email protected]
21. Restraint stress increases breast tumor growth and angiogenesis
Abstracts / Brain, Behavior, and Immunity 22 (2008) 1–7 parts showed a stress-related decline in performance. Gene eects on memory were seen only under stress whereby APOE e4+ subjects performed more poorly than their APOE e4 peers. Regression showed that the best predictors of the change in sIL-6r were gene status and change in perceived stress. Our results are the first demonstration of a stress-vulnerability eect of APOE e4 in young adult carriers. Possession of one or more copies of the gene may confer a dierential stress-vulnerability for cognition and sIL-6r, but not IL-6 or glucocorticoids. Further work is needed. doi:10.1016/j.bbi.2008.04.021
20. Social disruption enhances lung inflammation Jennifer Curry a, Michael Bailey b, Benjamin Bringardner c, Melissa Hunter a, John Sheridan b, Clay Marsh a,* a
Division of Pulmonary Medicine, The Ohio State University, USA Section of Oral Biology, College of Dentistry, The Institute for Behavioral Medicine Research, The Ohio State University, USA c Carolinas Medical Center, Charlotte, NC, USA * Corresponding author. E-mail: [email protected] b
Alterations in social environments aect the immune functions and behavior. In a model of social conflict, social disruption (SDR), cycles of attack and defeat are followed by increased anxiety-like behavior and enhanced secretion of proinflammatory cytokines from LPS-stimulated splenocytes. We hypothesize that SDR will cause in inflammatory response in the lung. C57BL/6 mice were subjected to six, 2 h sessions of SDR. SDR consists of introducing an aggressive intruder mouse to resident mice and leads to attack and defeat of the residents. Control mice are untouched in their home cages. Upon sacrifice, lungs were insulflated, and one lung was frozen protein analysis, performed with the Sircol collagen assay. The remaining lung was formalin-fixed and sectioned for IHC. A board-certified veterinary pathologist subjectively analyzed and scored H&E sections of lung tissue for the presence of lymphocyte and macrophage aggregates. SDR mice had greater lung inflammatory scores compared to control mice. We observed an increased number in neutrophils but not change in the number of macrophages in the lungs of SDR mice compared with control. While the macrophage number remained unchanged, we observed an increased expression of inducible nitric oxide sythase in the SDR mice while arginase expression was not aected. Additionally, lung collagen deposition was elevated twofold in SDR mice compared with control. These data illustrate the proinflammatory environment in the lungs created by social disruption stress. This state could produce detrimental eects, such as tissue damage, or beneficial eects, such as microbial killing.
5
In this study, we combine two well-defined animal models to examine the role that stress plays in carcinogenesis. We evaluate the aects of restraint stress eects in Polyoma middle T antigen (PyMT) mice, which spontaneously develop breast cancer and eventual pulmonary metastases. We hypothesize that stress will negatively aect the disease course in these mice. PyMT mice were subjected to 6 h of restraint stress per day from week 9 to 12 of age. Serum was taken pre- and post-stress to assess glucocorticoid levels. Breast tumors were examined for size by weight, angiogenesis by CD34 staining, and for macrophage, and NK cell presence by F4/80 staining and by assessing mRNA levels of NK1.1. Lungs were examined for pulmonary metastases by whole lung staining with Hematoxylin. Mice subjected to restraint stress had higher levels of serum corticosterone and a twofold increase in total tumor size. Restraint stress did not aect levels of pulmonary metastases. Restraint stress decreased the number of macrophages infiltrating the tumors; however, an increased number of NK cells were present within the tumors. Finally, stress increase angiogenesis within the breast tumors, as illustrated with an increased number of CD34-positive cells and a trend towards increased angiogenic factors and decreased anti-angiogenic factors present within the tumors. These results demonstrate that restraint stress increased breast tumor growth but did not aect pulmonary metastases in the PyMT mouse model. Restraint stress appeared to be increasing breast tumor size through increasing levels of angiogenesis within the tumors. doi:10.1016/j.bbi.2008.04.023
22. The association between fatigue, vital exhaustion and inflammatory markers in chronic heart failure Otto R.F. Smith *, Susanne S. Pedersen, Johan Denollet
TM
doi:10.1016/j.bbi.2008.04.022
21. Restraint stress increases breast tumor growth and angiogenesis Jennifer Curry a, Tim Eubank a, Ryan Roberts a, John Sheridan b, Clay Marsh a,* a
Division of Pulmonary Medicine, The Ohio State University, USA Section of Oral Biology, College of Dentistry, The Institute for Behavioral Medicine Research, The Ohio State University, USA * Corresponding author. E-mail: [email protected] b
Medical Psychology, Tilburg University, The Netherlands Corresponding author. E-mail: [email protected]
*
The aim of this prospective study was to examine whether fatigue and vital exhaustion predict inflammation at 12-month followup in chronic heart failure (CHF). One hundred and twenty-seven patients completed a questionnaire including the FAS (general fatigue), the DEFS (exertion fatigue), and the MQ (vital exhaustion), at baseline. Serum levels of TNF-±;, soluble TNF-±; receptors 1 (sTNFR1) and 2 (sTNF-R2), IL-1ra, and neopterin were measured by ELISA at 12 months. Exertion fatigue was associated with both sTNF-R1 (r = .26; p = .003) and sTNF-R2 (r = .26; p = .003), whereas vital exhaustion was only associated with sTNF-R1 (r = .27; p = .002). General fatigue was not associated with any of the biomarkers. After controlling for gender, age, etiology of CHF, and LVEF, the associations found in univariable analysis remained significant (exertion fatigue: bsTNF-R1 = .25, p = .008; bsTNF-R2 = .23, p = .01; vital exhaustion: bsTNF-R1 = .26, p = .003). PCA on the MQ resulted in three factors: general fatigue, depressive symptoms, and sleep difficulties. Depressive symptoms were significantly associated with sTNF-R1 (r = .32; p < .001) only. The other MQ subscales did not correlate with cytokine levels. Entering exertion fatigue and depressive symptoms simultaneously in a multivariable model revealed that depressive symptoms (b = .26, p = .006) were independently associated with sTNF-R1, and exertion fatigue (b = .21, p = .03) was independently associated with sTNF-R2. In conclusion, (1) exertion fatigue, but not general fatigue, was associated with increased inflammation in CHF, (2) exertion fatigue was primarily associated with sTNF-R2, and (3) the eect of vital exhaustion on sTNF-R1 could primarily be attributed to depressive symptoms. Future studies are warranted
20. Social disruption enhances lung inflammation Jennifer Curry a, Michael Bailey b, Benjamin Bringardner c, Melissa Hunter a, John Sheridan b, Clay Marsh a,* a
Division of Pulmonary Medicine, The Ohio State University, USA Section of Oral Biology, College of Dentistry, The Institute for Behavioral Medicine Research, The Ohio State University, USA c Carolinas Medical Center, Charlotte, NC, USA * Corresponding author. E-mail: [email protected] b
Alterations in social environments aect the immune functions and behavior. In a model of social conflict, social disruption (SDR), cycles of attack and defeat are followed by increased anxiety-like behavior and enhanced secretion of proinflammatory cytokines from LPS-stimulated splenocytes. We hypothesize that SDR will cause in inflammatory response in the lung. C57BL/6 mice were subjected to six, 2 h sessions of SDR. SDR consists of introducing an aggressive intruder mouse to resident mice and leads to attack and defeat of the residents. Control mice are untouched in their home cages. Upon sacrifice, lungs were insulflated, and one lung was frozen protein analysis, performed with the Sircol collagen assay. The remaining lung was formalin-fixed and sectioned for IHC. A board-certified veterinary pathologist subjectively analyzed and scored H&E sections of lung tissue for the presence of lymphocyte and macrophage aggregates. SDR mice had greater lung inflammatory scores compared to control mice. We observed an increased number in neutrophils but not change in the number of macrophages in the lungs of SDR mice compared with control. While the macrophage number remained unchanged, we observed an increased expression of inducible nitric oxide sythase in the SDR mice while arginase expression was not aected. Additionally, lung collagen deposition was elevated twofold in SDR mice compared with control. These data illustrate the proinflammatory environment in the lungs created by social disruption stress. This state could produce detrimental eects, such as tissue damage, or beneficial eects, such as microbial killing.
5
In this study, we combine two well-defined animal models to examine the role that stress plays in carcinogenesis. We evaluate the aects of restraint stress eects in Polyoma middle T antigen (PyMT) mice, which spontaneously develop breast cancer and eventual pulmonary metastases. We hypothesize that stress will negatively aect the disease course in these mice. PyMT mice were subjected to 6 h of restraint stress per day from week 9 to 12 of age. Serum was taken pre- and post-stress to assess glucocorticoid levels. Breast tumors were examined for size by weight, angiogenesis by CD34 staining, and for macrophage, and NK cell presence by F4/80 staining and by assessing mRNA levels of NK1.1. Lungs were examined for pulmonary metastases by whole lung staining with Hematoxylin. Mice subjected to restraint stress had higher levels of serum corticosterone and a twofold increase in total tumor size. Restraint stress did not aect levels of pulmonary metastases. Restraint stress decreased the number of macrophages infiltrating the tumors; however, an increased number of NK cells were present within the tumors. Finally, stress increase angiogenesis within the breast tumors, as illustrated with an increased number of CD34-positive cells and a trend towards increased angiogenic factors and decreased anti-angiogenic factors present within the tumors. These results demonstrate that restraint stress increased breast tumor growth but did not aect pulmonary metastases in the PyMT mouse model. Restraint stress appeared to be increasing breast tumor size through increasing levels of angiogenesis within the tumors. doi:10.1016/j.bbi.2008.04.023
22. The association between fatigue, vital exhaustion and inflammatory markers in chronic heart failure Otto R.F. Smith *, Susanne S. Pedersen, Johan Denollet
TM
doi:10.1016/j.bbi.2008.04.022
21. Restraint stress increases breast tumor growth and angiogenesis Jennifer Curry a, Tim Eubank a, Ryan Roberts a, John Sheridan b, Clay Marsh a,* a
Division of Pulmonary Medicine, The Ohio State University, USA Section of Oral Biology, College of Dentistry, The Institute for Behavioral Medicine Research, The Ohio State University, USA * Corresponding author. E-mail: [email protected] b
Medical Psychology, Tilburg University, The Netherlands Corresponding author. E-mail: [email protected]
*
The aim of this prospective study was to examine whether fatigue and vital exhaustion predict inflammation at 12-month followup in chronic heart failure (CHF). One hundred and twenty-seven patients completed a questionnaire including the FAS (general fatigue), the DEFS (exertion fatigue), and the MQ (vital exhaustion), at baseline. Serum levels of TNF-±;, soluble TNF-±; receptors 1 (sTNFR1) and 2 (sTNF-R2), IL-1ra, and neopterin were measured by ELISA at 12 months. Exertion fatigue was associated with both sTNF-R1 (r = .26; p = .003) and sTNF-R2 (r = .26; p = .003), whereas vital exhaustion was only associated with sTNF-R1 (r = .27; p = .002). General fatigue was not associated with any of the biomarkers. After controlling for gender, age, etiology of CHF, and LVEF, the associations found in univariable analysis remained significant (exertion fatigue: bsTNF-R1 = .25, p = .008; bsTNF-R2 = .23, p = .01; vital exhaustion: bsTNF-R1 = .26, p = .003). PCA on the MQ resulted in three factors: general fatigue, depressive symptoms, and sleep difficulties. Depressive symptoms were significantly associated with sTNF-R1 (r = .32; p < .001) only. The other MQ subscales did not correlate with cytokine levels. Entering exertion fatigue and depressive symptoms simultaneously in a multivariable model revealed that depressive symptoms (b = .26, p = .006) were independently associated with sTNF-R1, and exertion fatigue (b = .21, p = .03) was independently associated with sTNF-R2. In conclusion, (1) exertion fatigue, but not general fatigue, was associated with increased inflammation in CHF, (2) exertion fatigue was primarily associated with sTNF-R2, and (3) the eect of vital exhaustion on sTNF-R1 could primarily be attributed to depressive symptoms. Future studies are warranted