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145. Temporal associations between IL-6 and cortisol production in response to acute psychosocial stress
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B.A. Wentworth et al. / Brain, Behavior, and Immunity 26 (2012) S1–S50
cancer. Pro-inflammatory markers included IL-1beta, IL-6, TNFalpha, and C-reactive protein. All relationships were in the predicted direction, but inflammation was not associated with depression, fatigue, feelings of sickness, or processing speed. Cancer did not predict any outcomes. The relationship between COWAT and TNF-alpha approached significance (p = 0.057). Relationships between LNS and IL-1beta (p = 0.023), and PPT/IL-1beta and PPT/IL-6 (p < 0.01, p < 0.0001) were significant. The results suggest changes in blood inflammatory proteins in this population were not associated with changes in affect, but may be important predictors of working memory and fine motor skills. http://dx.doi.org/10.1016/j.bbi.2012.07.166
143. Interleukin-1R3 mediates interleukin-1 induced potassium current increase through fast activation of Akt kinase J. Qian, L. Zhu, Q. Li, N. Belevych, Q. Chen, F. Zhao, S. Herness, N. Quan Department of Oral Biology, Ohio State University, 304 Murray Hall, 460 Medical Center Drive, Columbus, OH 43210, United States Inflammatory cytokine interleukin-1 (IL-1) performs multiple functions in the central nervous system. The type 1 IL-1 receptor (IL-1R1) and the IL-1 receptor accesory protein (IL-1RAcP) form a functional IL-1 receptor complex that is thought to mediate most, if not all, IL-1-induced effects. Several recent studies, however, suggested the existence of a heretofore unidentified receptor for IL-1. In this study, we report that the IL-1R1 gene contains an internal promoter which drives the transcription of a shortened IL-1R1 mRNA. This mRNA is the template for an novel IL-1 receptor protein that is identical with IL-1R1 at the C-terminus, but with a shorter extracellular domain at the N-terminus. We have termed this molecule IL-1R3. The mRNA and protein for IL-1R3 are expressed in normal and two strains of commercially available IL-1R1 knockout mice. In addition, immunohistochemical staining indicates that IL-1R3 is expressed exclusively in neurons, whereas IL-1R1 can be localized in non-neuronal cells of the brain. Furthermore, IL-1 binds specifically to IL-1R3 when it is complexed with the newly discovered alternative IL-1 receptor accessory protein, IL-1RAcPb. Stimulation of neurons expressing both IL-1R3 and IL1RAcpb causes fast activation of the Akt kinase, which leads to an increase in voltage-gated potassium current. These results demonstrate IL-1R3/IL-1RAcPb complex mediates a unique subset of IL-1 activity. http://dx.doi.org/10.1016/j.bbi.2012.07.167
144. Adenosine receptor-dependent activation of caspase 1 impairs memory formation after hypoxia/reoxygenation G.S. Chiu, D. Chatterjee, P.T. Darmody, J.P. Walsh, R.W. Johnson, G.G. Freund University of Illinois at Urbana-Champaign, 1201 W, Gregory Dr., Rm 211, Urbana, IL 61801, United States The inability to create new memories is a critical adverse outcome during hypoxia and reoxygenation; however, the development and resolution of anterograde amnesia remains elusive. Brain-based IL-1 is suggested to be involved due to its role in both learning and brain injury. In our studies, we found that memory formation in mice exposed to hypoxia/reoxygenation was impaired for up to 6 h. Recovery in the ability to form new memories was accelerated in IL-1 receptor 1 knockout mice, in mice receiving IL-1 receptor antagonist (IL-1RA) and in mice given the caspase 1 inhibitor, Ac-YVADCMK. Similarly, the administration of the adenosine receptor (AR) antagonist, caffeine, expedited recovery from anterograde amnesia.
Furthermore, hypoxia/reoxygenation more than doubled brain caspase 1 activity, while adenosine alone was able to elicit a similar response. This reoxygenation-dependent activation of caspase 1 was prevented by administration of either caffeine or by targeted antagonism of A1/A2A ARs. These findings suggest that anterograde amnesia after hypoxia/reoxygenation is reliant, in part, on IL-1beta generated by AR-dependent activation of caspase 1 after reoxygenation. http://dx.doi.org/10.1016/j.bbi.2012.07.168
145. Temporal associations between IL-6 and cortisol production in response to acute psychosocial stress C.E. Gawuga a, A.R. Tyrka b,c, L.H. Price b,c, L.L. Carpenter b,c a Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, 171 Meeting Street, Box G-8013, Providence, RI 02906, United States b Mood Disorders Research Program, Laboratory for Clinical Neuroscience, Butler Hospital, Providence, RI, United States c Department of Psychiatry and Human Behavior, The Warren Alpert Medical School of Brown University, Providence, RI, United States
Objective: . Although it is known that there is a temporal, regulatory relationship between cortisol and IL-6, it has not yet been established that such a relationship extends to the neuroendocrine and immune responses to acute psychosocial stress. Methods. Healthy adult participants underwent the Trier Social Stress Test. IV blood samples were collected before and after the test (time points 0, +15, +30, +45, +60, +75, +90), and emotional ratings were completed. Results. Lower plasma cortisol concentration at time point 0 was correlated with higher IL-6 concentrations at time points +60 and +75 (p = 0.001; p = 0.001). Lower plasma cortisol at time point +15 was also correlated with higher IL-6 at time points +60 and +75 (p < 0.05; p = 0.008). Linear regression showed that lower cortisol levels at time point 0 predicted plasma IL-6 at time point +60 (p = 0.006). Other predictors of IL-6 at +60 were BMI (p = 0.002), gender (p = 0.027), and change in depressive mood from time 0 to +30 (p = 0.015). Only BMI predicted IL-6 at time point +75 (p < 0.001). Conclusion. Subjects with lower baseline plasma cortisol concentrations generated a greater IL-6 response one hour after initiation of the TSST. Greater change in depressive mood, higher BMI, and female gender also contributed to elevated IL-6 response to the TSST. These results suggest that the temporal regulatory relationship between cortisol and IL-6 persists even in the context of acute psychosocial stress. http://dx.doi.org/10.1016/j.bbi.2012.07.169
146. Depressive symptoms and cardiovascular risk B.A. Wentworth a, M.N. Iqbal a,b, K. Wachmann a, L.S. Redwine a, A.S. Maisel a,b, P.J. Mills a a
University of California, San Diego, Department of Psychiatry and Behavioral Medicine, 9500 Gilman Drive, MC0804 La Jolla, CA 92093, United States b Veteran’s Healthcare Administration San Diego, United States Background: Increased cardiovascular risk in those with depressive symptoms is well-documented, notably increased mortality, rehospitalizations, and adverse cardiac events. B-type natriuretic peptide (BNP) is used as a prognostic marker of cardiovascular disease risk for heart failure. We seek to elucidate whether BNP and other cardiac parameters are associated with depressive symptoms to determine biological factors that may prevent adverse cardiac outcomes. Methods: Patients receiving echocardiograms between
B.A. Wentworth et al. / Brain, Behavior, and Immunity 26 (2012) S1–S50
cancer. Pro-inflammatory markers included IL-1beta, IL-6, TNFalpha, and C-reactive protein. All relationships were in the predicted direction, but inflammation was not associated with depression, fatigue, feelings of sickness, or processing speed. Cancer did not predict any outcomes. The relationship between COWAT and TNF-alpha approached significance (p = 0.057). Relationships between LNS and IL-1beta (p = 0.023), and PPT/IL-1beta and PPT/IL-6 (p < 0.01, p < 0.0001) were significant. The results suggest changes in blood inflammatory proteins in this population were not associated with changes in affect, but may be important predictors of working memory and fine motor skills. http://dx.doi.org/10.1016/j.bbi.2012.07.166
143. Interleukin-1R3 mediates interleukin-1 induced potassium current increase through fast activation of Akt kinase J. Qian, L. Zhu, Q. Li, N. Belevych, Q. Chen, F. Zhao, S. Herness, N. Quan Department of Oral Biology, Ohio State University, 304 Murray Hall, 460 Medical Center Drive, Columbus, OH 43210, United States Inflammatory cytokine interleukin-1 (IL-1) performs multiple functions in the central nervous system. The type 1 IL-1 receptor (IL-1R1) and the IL-1 receptor accesory protein (IL-1RAcP) form a functional IL-1 receptor complex that is thought to mediate most, if not all, IL-1-induced effects. Several recent studies, however, suggested the existence of a heretofore unidentified receptor for IL-1. In this study, we report that the IL-1R1 gene contains an internal promoter which drives the transcription of a shortened IL-1R1 mRNA. This mRNA is the template for an novel IL-1 receptor protein that is identical with IL-1R1 at the C-terminus, but with a shorter extracellular domain at the N-terminus. We have termed this molecule IL-1R3. The mRNA and protein for IL-1R3 are expressed in normal and two strains of commercially available IL-1R1 knockout mice. In addition, immunohistochemical staining indicates that IL-1R3 is expressed exclusively in neurons, whereas IL-1R1 can be localized in non-neuronal cells of the brain. Furthermore, IL-1 binds specifically to IL-1R3 when it is complexed with the newly discovered alternative IL-1 receptor accessory protein, IL-1RAcPb. Stimulation of neurons expressing both IL-1R3 and IL1RAcpb causes fast activation of the Akt kinase, which leads to an increase in voltage-gated potassium current. These results demonstrate IL-1R3/IL-1RAcPb complex mediates a unique subset of IL-1 activity. http://dx.doi.org/10.1016/j.bbi.2012.07.167
144. Adenosine receptor-dependent activation of caspase 1 impairs memory formation after hypoxia/reoxygenation G.S. Chiu, D. Chatterjee, P.T. Darmody, J.P. Walsh, R.W. Johnson, G.G. Freund University of Illinois at Urbana-Champaign, 1201 W, Gregory Dr., Rm 211, Urbana, IL 61801, United States The inability to create new memories is a critical adverse outcome during hypoxia and reoxygenation; however, the development and resolution of anterograde amnesia remains elusive. Brain-based IL-1 is suggested to be involved due to its role in both learning and brain injury. In our studies, we found that memory formation in mice exposed to hypoxia/reoxygenation was impaired for up to 6 h. Recovery in the ability to form new memories was accelerated in IL-1 receptor 1 knockout mice, in mice receiving IL-1 receptor antagonist (IL-1RA) and in mice given the caspase 1 inhibitor, Ac-YVADCMK. Similarly, the administration of the adenosine receptor (AR) antagonist, caffeine, expedited recovery from anterograde amnesia.
Furthermore, hypoxia/reoxygenation more than doubled brain caspase 1 activity, while adenosine alone was able to elicit a similar response. This reoxygenation-dependent activation of caspase 1 was prevented by administration of either caffeine or by targeted antagonism of A1/A2A ARs. These findings suggest that anterograde amnesia after hypoxia/reoxygenation is reliant, in part, on IL-1beta generated by AR-dependent activation of caspase 1 after reoxygenation. http://dx.doi.org/10.1016/j.bbi.2012.07.168
145. Temporal associations between IL-6 and cortisol production in response to acute psychosocial stress C.E. Gawuga a, A.R. Tyrka b,c, L.H. Price b,c, L.L. Carpenter b,c a Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, 171 Meeting Street, Box G-8013, Providence, RI 02906, United States b Mood Disorders Research Program, Laboratory for Clinical Neuroscience, Butler Hospital, Providence, RI, United States c Department of Psychiatry and Human Behavior, The Warren Alpert Medical School of Brown University, Providence, RI, United States
Objective: . Although it is known that there is a temporal, regulatory relationship between cortisol and IL-6, it has not yet been established that such a relationship extends to the neuroendocrine and immune responses to acute psychosocial stress. Methods. Healthy adult participants underwent the Trier Social Stress Test. IV blood samples were collected before and after the test (time points 0, +15, +30, +45, +60, +75, +90), and emotional ratings were completed. Results. Lower plasma cortisol concentration at time point 0 was correlated with higher IL-6 concentrations at time points +60 and +75 (p = 0.001; p = 0.001). Lower plasma cortisol at time point +15 was also correlated with higher IL-6 at time points +60 and +75 (p < 0.05; p = 0.008). Linear regression showed that lower cortisol levels at time point 0 predicted plasma IL-6 at time point +60 (p = 0.006). Other predictors of IL-6 at +60 were BMI (p = 0.002), gender (p = 0.027), and change in depressive mood from time 0 to +30 (p = 0.015). Only BMI predicted IL-6 at time point +75 (p < 0.001). Conclusion. Subjects with lower baseline plasma cortisol concentrations generated a greater IL-6 response one hour after initiation of the TSST. Greater change in depressive mood, higher BMI, and female gender also contributed to elevated IL-6 response to the TSST. These results suggest that the temporal regulatory relationship between cortisol and IL-6 persists even in the context of acute psychosocial stress. http://dx.doi.org/10.1016/j.bbi.2012.07.169
146. Depressive symptoms and cardiovascular risk B.A. Wentworth a, M.N. Iqbal a,b, K. Wachmann a, L.S. Redwine a, A.S. Maisel a,b, P.J. Mills a a
University of California, San Diego, Department of Psychiatry and Behavioral Medicine, 9500 Gilman Drive, MC0804 La Jolla, CA 92093, United States b Veteran’s Healthcare Administration San Diego, United States Background: Increased cardiovascular risk in those with depressive symptoms is well-documented, notably increased mortality, rehospitalizations, and adverse cardiac events. B-type natriuretic peptide (BNP) is used as a prognostic marker of cardiovascular disease risk for heart failure. We seek to elucidate whether BNP and other cardiac parameters are associated with depressive symptoms to determine biological factors that may prevent adverse cardiac outcomes. Methods: Patients receiving echocardiograms between