- Email: [email protected]
19. Antidepressants, but not antipsychotics, inhibits glucocorticoid receptor function in vitro – involvement of P38 mapk
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Abstracts / Brain, Behavior, and Immunity 23 (2009) S25–S64
chart extraction. Correlations between CRF, E3, and birth outcome in response to stress, social support, and distress were evaluated. Preliminary data suggests elevated CRF early in pregnancy is linked to lower gestational age at birth accompanied by lower 1-min APGAR scores. Furthermore, increased levels of CRF late in pregnancy were associated with lower levels of social support and distress late in pregnancy. This relationship was positively linked with higher TNF-a and CRP in late pregnancy. Elevated E3 related to lower IL-6 late in pregnancy and higher reports of stress in early and late pregnancy. Collectively these data indicate prenatal stress affects maternal and fetal endocrine function and birth outcome. doi:10.1016/j.bbi.2009.06.022
18. Immune cells produce catecholamines during arthritis: New aspects of neuro-immunological response S. Capellino, K. Weber, C. Wolff, A. Fassold, R.H. Straub University Hospital Regensburg, Internal Medicine I - Lab. of Neuroendocrinoimmunology, Franz Josef Strauss Allee 11, Regensburg, XX 93042, Germany Introduction: In our previous study, we demonstrated that synovial cells produce catecholamines during chronic inflammation such as rheumatoid arthritis, and that catecholamine modulation reduced TNF release in primary synovial cells. Also in vivo on DBA/1J arthritis mice we confirmed the beneficial effect of catecholamine modulation on arthritis. Aim: To understand whether catecholamine-producing cells differentiate in synovial tissue or not, and when they start to play a role in the inflammatory response. Methods: Collagen type-II induced arthritis model was used in DBA/1J mice. Twenty mice were immunized and 20 mice served as controls. At day 0–7–14–21–28–35–42–49–60 and 80 after first immunization, two mice of each group were sacrificed. Bone marrow, paws and spleen were stained by immunofluorescence to detect vesicular monoamine transporter-2 (VMAT-2). Density of positive cells was averaged and expressed per square millimeter. Results: Twenty-one days after first immunization, the amount of VMAT-2 positive cells in bone marrow started to be significantly higher in arthritic mice compared to controls. In the spleen, the amount of VMAT-2 positive cells was significantly higher in arthritic mice from day 49. First results on the paws showed that VMAT-2 positive cells appear later during the chronic phase. Conclusions: These results demonstrate that catecholamines are produced and stored by immune cells in the early asymptomatic phase of arthritis. Thus, they might play a crucial role in immunomodulation. doi:10.1016/j.bbi.2009.06.023
19. Antidepressants, but not antipsychotics, inhibits glucocorticoid receptor function in vitro – involvement of P38 mapk L. Carvalho a, B. Garner b, C.M. Pariante a a Institute of Psychiatry, Kings College London, Psychological Medicine, 125 Coldharbour Lane, London, Se5 9NU, UK b Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Royal Belbourne Hospital, Belbourne, Australia
Clinical studies have demonstrated an impairment of glucocorticoid receptor (GR)-mediated negative feedback on the hypotha-
lamic–pituitary–adrenal (HPA) axis in patients with major depression (GR resistance), and its resolution by antidepressant treatment. To further investigate the effect of antidepressants on GR function, we have evaluated the effect of clomipramine (CMI), amitriptiline (AMY), sertraline (SER), paroxetine (PAR) and venlafaxine (VEN) on glucocorticoid inhibition of lypopolysaccharide (LPS)-stimulated interleukin-6 (IL-6) levels. Compared to vehicle-treated cells, antidepressants inhibited dexamethasone (DEX) inhibition of LPS-stimulated IL-6 levels (DEX 10 nM and CMI, p = 0.03; DEX 10 nM and AMY, p = 0.02; DEX 10 nM and SER, p = 0.007; DEX 10 nM and VEN, p = 0.05). This effect was specific to antidepressants, as the antipsychotics haloperidol (HAL 10 lM) and risperidone (RIS 10 lM) had no effect (DEX 10 nM, RIS and HAL, F(1, 3) = 0.39, p = 0.68). Clomipramine also inhibited GR function in the presence of corticosterone (F(1, 8) = 12.73, p = 0.0001), suggesting no involvement of membrane steroid transporters. Furthermore, rolipram a phosphodiesterase (PDE) type 4 inhibitor that antagonizes cAMP breakdown synergized with clomipramine and inhibited further GR function (F[1, 3] = 7.613, p = 0.001). Finally, the selective p38 MAPK activator inhibited the effect of antidepressants on GR function. These findings indicate that molecular pathways including cAMP and p38 MAPK are involved on the effect of antidepressants on GR function (F[1, 4] = 2.85, p = 0.04). Research in this field will lead to new insights into the pathophysiology and treatment of affective disorders. doi:10.1016/j.bbi.2009.06.024
20. Depressive symptoms predict exaggerated inflammatory responses to an in vivo immune challenge among pregnant women L.M. Christian, A. Franco, J.D. Iams, J. Sheridan, R. Glaser The Ohio State University, Psychiatry, 1670 Upham Drive, Columbus, OH 43210, United States Stress and depressive symptoms predict exaggerated inflammatory responses to a biological challenge in nonpregnant humans and animals. The extent to which these findings extend to pregnancy is unknown because the immune system exhibits substantial changes during pregnancy. However, inflammatory responses to infectious agents play a causal role in the development of gestational hypertension and risk for preterm birth. Thus, depressive symptoms may increase susceptibility to these outcomes via sensitization of inflammatory processes. This study tested the hypothesis that depressive symptoms would predict an exaggerated proinflammatory response to an in vivo antigen challenge, influenza virus vaccination, during pregnancy. Depressive symptoms and serum levels of macrophage migration inhibitory factor (MIF) were assessed in 22 pregnant women at two timepoints: baseline and one week after influenza virus vaccination. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CESD). Serum levels of MIF were determined using a high sensitivity immunoassay. As compared to those in the lowest tertile of CES-D scores, those in the highest tertile exhibited significantly higher levels of MIF one week after vaccination (p = .03). Depressive symptoms predicted exaggerated MIF production following influenza virus vaccination during pregnancy. These data support the hypothesis that depressive symptoms are associated with sensitization of the inflammatory response during pregnancy. Thus, women with greater depressive symptoms during pregnancy may be more vulnerable to negative sequelae of infectious illness. doi:10.1016/j.bbi.2009.06.025
Abstracts / Brain, Behavior, and Immunity 23 (2009) S25–S64
chart extraction. Correlations between CRF, E3, and birth outcome in response to stress, social support, and distress were evaluated. Preliminary data suggests elevated CRF early in pregnancy is linked to lower gestational age at birth accompanied by lower 1-min APGAR scores. Furthermore, increased levels of CRF late in pregnancy were associated with lower levels of social support and distress late in pregnancy. This relationship was positively linked with higher TNF-a and CRP in late pregnancy. Elevated E3 related to lower IL-6 late in pregnancy and higher reports of stress in early and late pregnancy. Collectively these data indicate prenatal stress affects maternal and fetal endocrine function and birth outcome. doi:10.1016/j.bbi.2009.06.022
18. Immune cells produce catecholamines during arthritis: New aspects of neuro-immunological response S. Capellino, K. Weber, C. Wolff, A. Fassold, R.H. Straub University Hospital Regensburg, Internal Medicine I - Lab. of Neuroendocrinoimmunology, Franz Josef Strauss Allee 11, Regensburg, XX 93042, Germany Introduction: In our previous study, we demonstrated that synovial cells produce catecholamines during chronic inflammation such as rheumatoid arthritis, and that catecholamine modulation reduced TNF release in primary synovial cells. Also in vivo on DBA/1J arthritis mice we confirmed the beneficial effect of catecholamine modulation on arthritis. Aim: To understand whether catecholamine-producing cells differentiate in synovial tissue or not, and when they start to play a role in the inflammatory response. Methods: Collagen type-II induced arthritis model was used in DBA/1J mice. Twenty mice were immunized and 20 mice served as controls. At day 0–7–14–21–28–35–42–49–60 and 80 after first immunization, two mice of each group were sacrificed. Bone marrow, paws and spleen were stained by immunofluorescence to detect vesicular monoamine transporter-2 (VMAT-2). Density of positive cells was averaged and expressed per square millimeter. Results: Twenty-one days after first immunization, the amount of VMAT-2 positive cells in bone marrow started to be significantly higher in arthritic mice compared to controls. In the spleen, the amount of VMAT-2 positive cells was significantly higher in arthritic mice from day 49. First results on the paws showed that VMAT-2 positive cells appear later during the chronic phase. Conclusions: These results demonstrate that catecholamines are produced and stored by immune cells in the early asymptomatic phase of arthritis. Thus, they might play a crucial role in immunomodulation. doi:10.1016/j.bbi.2009.06.023
19. Antidepressants, but not antipsychotics, inhibits glucocorticoid receptor function in vitro – involvement of P38 mapk L. Carvalho a, B. Garner b, C.M. Pariante a a Institute of Psychiatry, Kings College London, Psychological Medicine, 125 Coldharbour Lane, London, Se5 9NU, UK b Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Royal Belbourne Hospital, Belbourne, Australia
Clinical studies have demonstrated an impairment of glucocorticoid receptor (GR)-mediated negative feedback on the hypotha-
lamic–pituitary–adrenal (HPA) axis in patients with major depression (GR resistance), and its resolution by antidepressant treatment. To further investigate the effect of antidepressants on GR function, we have evaluated the effect of clomipramine (CMI), amitriptiline (AMY), sertraline (SER), paroxetine (PAR) and venlafaxine (VEN) on glucocorticoid inhibition of lypopolysaccharide (LPS)-stimulated interleukin-6 (IL-6) levels. Compared to vehicle-treated cells, antidepressants inhibited dexamethasone (DEX) inhibition of LPS-stimulated IL-6 levels (DEX 10 nM and CMI, p = 0.03; DEX 10 nM and AMY, p = 0.02; DEX 10 nM and SER, p = 0.007; DEX 10 nM and VEN, p = 0.05). This effect was specific to antidepressants, as the antipsychotics haloperidol (HAL 10 lM) and risperidone (RIS 10 lM) had no effect (DEX 10 nM, RIS and HAL, F(1, 3) = 0.39, p = 0.68). Clomipramine also inhibited GR function in the presence of corticosterone (F(1, 8) = 12.73, p = 0.0001), suggesting no involvement of membrane steroid transporters. Furthermore, rolipram a phosphodiesterase (PDE) type 4 inhibitor that antagonizes cAMP breakdown synergized with clomipramine and inhibited further GR function (F[1, 3] = 7.613, p = 0.001). Finally, the selective p38 MAPK activator inhibited the effect of antidepressants on GR function. These findings indicate that molecular pathways including cAMP and p38 MAPK are involved on the effect of antidepressants on GR function (F[1, 4] = 2.85, p = 0.04). Research in this field will lead to new insights into the pathophysiology and treatment of affective disorders. doi:10.1016/j.bbi.2009.06.024
20. Depressive symptoms predict exaggerated inflammatory responses to an in vivo immune challenge among pregnant women L.M. Christian, A. Franco, J.D. Iams, J. Sheridan, R. Glaser The Ohio State University, Psychiatry, 1670 Upham Drive, Columbus, OH 43210, United States Stress and depressive symptoms predict exaggerated inflammatory responses to a biological challenge in nonpregnant humans and animals. The extent to which these findings extend to pregnancy is unknown because the immune system exhibits substantial changes during pregnancy. However, inflammatory responses to infectious agents play a causal role in the development of gestational hypertension and risk for preterm birth. Thus, depressive symptoms may increase susceptibility to these outcomes via sensitization of inflammatory processes. This study tested the hypothesis that depressive symptoms would predict an exaggerated proinflammatory response to an in vivo antigen challenge, influenza virus vaccination, during pregnancy. Depressive symptoms and serum levels of macrophage migration inhibitory factor (MIF) were assessed in 22 pregnant women at two timepoints: baseline and one week after influenza virus vaccination. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CESD). Serum levels of MIF were determined using a high sensitivity immunoassay. As compared to those in the lowest tertile of CES-D scores, those in the highest tertile exhibited significantly higher levels of MIF one week after vaccination (p = .03). Depressive symptoms predicted exaggerated MIF production following influenza virus vaccination during pregnancy. These data support the hypothesis that depressive symptoms are associated with sensitization of the inflammatory response during pregnancy. Thus, women with greater depressive symptoms during pregnancy may be more vulnerable to negative sequelae of infectious illness. doi:10.1016/j.bbi.2009.06.025