Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Formation of reactive oxygen intermediates (ROI) after oxidative stress has been shown to be an activation signal for T lymphocytes, e.g., expression of IL-2 and its receptor are induced. These ROI-induced effects can, to a large extent, be attributed to the activation of the transcription factor NF-kappaB. Now we have examined whether naive and memory T lymphocytes differ in their sensitivity to ROI-mediated signals. When CD45RA+ (naive) and CD45RO+ (memory) T lymphocytes were directly stimulated with H2O2, NF-kappaB nuclear translocation was stronger in naive cells than in memory cells and it could be induced with lower doses. The composition of the induced nuclear NF-kappaB (levels of p50 and RelA proteins) was similar in these cell types. The magnitude and kinetics of intracellular ROI were similar, suggesting that there were no differences in ROI-forming mechanisms or antioxidative capacities. The probable regulatory point was the cytoplasmic IkappaB inhibitor: in CD45RA+ cells, H2O2 caused a more profound depression in the levels of IkappaB alpha. These findings indicate that T cells representing different activation and/or differentiation stages can be differentially responsive to ROI-mediated signals.
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PMID:Naive (CD45RA+) T lymphocytes are more sensitive to oxidative stress-induced signals than memory (CD45RO+) cells. 891 88

CD4-targeted therapy with a nondepleting RIB-5/2 mAb abrogates accelerated (< 36 h) rejection in presensitized LEW rats and results in permanent acceptance of LBNF1 cardiac allografts in conjunction with the features of infectious tolerance. This study examined the role and functional significance of the Th1 and Th2 cytokine network and systemic host allospecific Ab (allo-Ab) responses in the development of the infectious tolerance pathway in this model. Long term survival of cardiac transplants in rats treated with the tolerizing RIB-5/2 mAb regimen was accompanied by profound depression of Th1 (IL-2 and IFN-gamma) and Th2 (IL-4, IL-10) cytokines at the graft site, as shown by competitive template reverse transcription-PCR and immunohistochemistry. In contrast, the expression of Th2-type cytokines was selectively up-regulated after transfer of infectious tolerance by spleen cells into new generations of primary and secondary test recipients. Donor-specific circulating IgM allo-Ab responses were diminished throughout, and the switch from IgM to IgG allo-Ab was completely prevented in tolerant hosts, as shown by flow cytometry. The demonstration that treatment with cytolytic anti-CD4, but not anti-CD8, mAb recreated rejection of test cardiac allografts with simultaneous down-regulation of IL-4 mRNA/protein expression underlines the importance of this cytokine in the development of infectious tolerance. Hence, this report documents distinct cytokine elaboration patterns in animals tolerized by CD4-targeted therapy compared with those rendered tolerant by putative regulatory Th2-like cells. The mechanism of tolerance in anti-CD4 mAb-treated hosts appears distinct from that operating in the absence of mAb, when the tolerant state is being transferred in an infectious manner to new cohorts of test recipients.
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PMID:Type 2 helper T cell-type cytokines and the development of "infectious" tolerance in rat cardiac allograft recipients. 902 92

Mechanisms responsible for the increase in malaria susceptibility during pregnancy, and in particular during the first pregnancy, have not been elucidated. T and B cell responses to leucoagglutinin, bacille Calmette-Guerin (BCG) and to six Plasmodium falciparum antigens were longitudinally investigated in 33 pregnant women during their first pregnancy, after delivery, and during second pregnancy. Parasitological data obtained from the same women during and after the first pregnancy demonstrated the higher risk of P. falciparum infection during this pregnancy. Plasma levels of antibodies to Pf155/ RESA were lower during pregnancy than after delivery. Conversely, antibodies to P. falciparum asexual blood stages were higher during pregnancy than after delivery, suggesting that during pregnancy the regulation of antibody production may be variously impaired depending upon the antigens. The most striking finding of the present study is the impairment of the IL-2 cellular response during the first pregnancy. Conversely, proliferative responses, as well as IL-4 and interferon-gamma (IFN-gamma) responses, were either unaffected or moderately enhanced. No difference in humoral and cellular responses was observed between first and second pregnancy. The impairment of the IL-2 responses involved the response to malaria peptides and proteins, as well as the response to non-malarial antigens and to the mitogen leucoagglutinin. Thus, the alteration of malaria immunity might rather fall into the general frame of the depression of cellular immunity during pregnancy than involve a specific malaria phenomenon.
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PMID:Immune response to Plasmodium falciparum antigens in Cameroonian primigravidae: evolution after delivery and during second pregnancy. 906 18

There is a strong interrelationship between the immune system, the central nervous system and psychological processes that are suggested to play a pivotal role in the pathogenesis of psychiatric disorders. In schizophrenia and depression, activation of the immune system has been observed repeatedly. Cytokines play a key role in immune activation. They are actively transported into the CNS, but also released from activated glia cells. Cytokines activate glia cells in the CNS to produce other cytokines, and a cascade of cytokine effects may be initiated by this mechanisms. During the past few years, the influence of the cytokines on dopaminergic, noradrenergic and serotonergic neurotransmission and also on the hormones of the hypothalamus-pituitary-adrenal axis has been elucidated. It suggests a pivotal role in psychological processes and psychiatric disorders. For example, in schizophrenia the IL-2 cerebrospinal fluid concentration shows a stronger relationship to the relapse probability than catecholamine metabolites. Although the hypersecretion of IL-2 in schizophrenia and of IL-6 in depression are suggested to play key roles for these disorders, a specificity of certain cytokines for certain psychiatric disorders seems unlikely. Psychomotor, sleep and sickness behavior are influenced by IL-1, disturbances of memory and attention by IL-2, but also by TNF-alpha. From the distribution of cytokine receptors in the CNS conclusions can be drawn regarding the influence of cytokines on psychological processes. The finding that norepinephrine stimulates activated astrocytes to produce IL-6 implies that the cytokine cascade may be activated by neuronal processes under certain conditions. This can lead to a molecular biological explanation of the influences of stress on the immune system. Lastly, influences of the cytokines on blood-brain barrier disturbances and further consequences resulting from the role of the cytokine network in the CNS are discussed.
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PMID:[Role of the cytokine network in the CNS and psychiatric disorders]. 913 17

Previous research in this laboratory has shown that major depression is accompanied by decreased serum activity of dipeptidyl peptidase IV (DPP IV), a serine protease that cleaves N terminal dipeptides from peptides with penultimate proline or alanine. DPP IV is involved in the metabolism of peptides, T cell activation and proliferation, including the production of cytokines, such as interleukin-1 (IL-1) and IL-2. The aim of this study was to examine (i) serum DPP IV activity in major and treatment resistant depression (TRD) in relation to other established immune and inflammatory markers of that illness, and (ii) the effects of antidepressive treatment on DPP IV activity. Serum DPP IV activity was significantly lower in major depression and TRD than in normal controls. In normal and major depressed subjects, there were significant and positive relationships between serum DPP IV activity and total serum protein, serum albumin, zinc, iron and transferrin. In the group of depressed subjects, there were significant and positive relationships between serum DPP IV activity and number of CD4+T cells and CD4+/CD8+ T cell ratio. There were no significant effects of subchronic treatment with antidepressants on serum DPP IV activity. The findings suggest that: (i) lower serum DPP activity may occur in chronic depression, TRD as well as in the acute phase of major depression; (ii) lower serum DPP IV accompanies the 'chronic' acute phase response in depression; and (iii) serum DPP IV activity is tightly coupled to increased number of CD4+ T cells in depressed subjects, but not in normal controls. Our results do not exclude the possible effects of longer-term treatment with antidepressants on serum DPP-IV activity.
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PMID:Lower serum dipeptidyl peptidase IV activity in treatment resistant major depression: relationships with immune-inflammatory markers. 914 29

The effects of orally administered sodium nitrite (20 mg NaNO2/kg b. w) on the responses of T and B lymphocytes collected from the mesenteric lymph nodes were studied in resistant AKR/J, H-2(k) haplotype mice infected with Trichinella spiralis nematode. On days 6, 9, and 12 postinfection, the mesenteric lymph node cells (MLNC) were collected from the mice and assayed for lymphocyte subsets (CD4(+), CD8(+), B220(+)), cytokines (IL-2, IL-5), and INF-gamma. At the same time, the number of adult worms in the small intestine were counted. Infection of the nitrite-treated mice with T. spiralis L1 larvae caused a marked increase in the number of adult worms in the small intestine. However, preincubation of T. spiralis L1 larvae with nitrite before infecting the mice resulted in a significant reduction in the number of adult worms (p < 0.05). Preincubation of T. spiralis L1 larvae with nitrite also caused an increase in the number of CD4(+) and CD8(+) cells as well as IL-2, IL-5, and INF-gamma levels. An increased level of CD8(+) subsets and a depression of IL-2 and IL-5 production by MLNC were observed in mice infected with larvae without nitrite pretreatment. Since supplementary rIL-1alpha was found to alter INF-gamma secretion by MLNC in vitro, the pattern of MLNC proliferation was examined further with the nitrite-treated mice. Sodium nitrite increased thymidine incorporation into the MLNC. However, INF-gamma production was not enhanced when rIL-1alpha was added to the MLNC culture obtained from nitrite-treated mice.
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PMID:Nitrite mediated T lymphocyte responses in the intestinal immune system of mice infected with Trichinella spiralis nematode. 917 17

Studies indicate that the liver, in particular the Kupffer cells, appear to be key contributors in the systemic inflammatory mediator response associated with shock and sepsis. Although several of these agents have been implicated as mediators of depressed immunoresponsiveness observed during sepsis, it remains unknown whether or not mediators released specifically by Kupffer cells play any significant role in producing the cellular dysfunction in distant organs. The aim of this study, therefore, was to determine whether or not acute Kupffer cell reduction before the onset of sepsis would protect splenic lymphocyte function. Kupffer cell number was reduced by prior (48 hours) treatment of mice with gadolinium chloride (GdCl2, 10 mg/kg of body weight, intravenously) or saline vehicle. Animals were then subjected to either sham-CLP (sham) or polymicrobial sepsis in the form of cecal ligation and puncture (CLP). Plasma and splenocytes were harvested at 2 or 24 hours after CLP. Splenocyte cultures were exposed to 2.5 micrograms concanavalin A/mL to assess their ability to release lymphokines. Cytokine (interleukin (IL)-2, IL-6, interferon-gamma, tumor necrosis factor-alpha) concentration in plasma or cell supernatants was assessed by bioassay. The results indicated that GdCl2 treated mice exhibited a marked reduction in circulating IL-6 levels at both 2 and 24 hours after CLP. Furthermore, the reduction of Kupffer cell number before the onset of sepsis completely prevented the depression of splenocyte IL-2 and interferon-gamma release, capacity. Thus mediators released by Kupffer cells during the systemic inflammatory response to polymicrobial sepsis play a significant role in producing immune dysfunction in resident splenic lymphocytes. In view of this, it appears that modulation of Kupffer cell hyperactivity during sepsis may be a novel approach for maintaining distant organ host defense mechanisms.
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PMID:Mechanism of splenic immunosuppression during sepsis: key role of Kupffer cell mediators. 919 70

Stressful environmental conditions are a major determinant of immune reactivity. This effect is pronounced in Australian National Antarctic Research Expedition populations exposed to prolonged periods of isolation in the Antarctic. Alterations of T cell function, including depression of cutaneous delayed-type hypersensitivity responses and a peak 48.9% reduction of T cell proliferation to the mitogen phytohaemagglutinin, were documented during a 9-month period of isolation. T cell dysfunction was mediated by changes within the peripheral blood mononuclear cell compartment, including a paradoxical atypical monocytosis associated with altered production of inflammatory cytokines. There was a striking reduction in the production by peripheral blood mononuclear cells of the predominant pro-inflammatory monokine TNF-alpha and changes were also detected in the production of IL-1, IL-2, IL-6, IL-1ra and IL-10. Prolonged Antarctic isolation is also associated with altered latent herpesvirus homeostasis, including increased herpesvirus shedding and expansion of the polyclonal latent Epstein-Barr virus-infected B cell population. These findings have important long-term health implications.
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PMID:Antarctic isolation: immune and viral studies. 924 93

Recent studies indicate beneficial effects of androgen depletion in male mice, before trauma-hemorrhage on cell-mediated immunity following soft-tissue trauma and hemorrhagic shock. Nonetheless, it remains unknown whether androgen receptor blockade following the insult has any salutary effects. To study this, male C3H/HeN mice were either sham-operated or subjected to soft-tissue trauma (i.e., 2.5 cm midline laparotomy) followed by hemorrhagic shock (blood pressure 35 +/- 5 mmHg for 90 min) and then adequately resuscitated (shed blood and lactated Ringer's). Immediately after the completion of resuscitation, as well as 24 and 48 h thereafter, the animals received either vehicle, 10 mg/kg body weight (BW) flutamide or 25 mg/kg BW flutamide subcutaneously. At 72 h after resuscitation, all animals were killed. The spleens and peritoneal macrophages (M phi) were then harvested and cultures established to determine IL-2 and IL-3 release, splenocyte proliferative capacity, as well as splenic and peritoneal M phi IL-1 release. Moreover, plasma testosterone and corticosterone levels were measured. Our results indicate that trauma-hemorrhage resulted in significant depression of splenocyte and M phi functions in vehicle-treated and animals receiving 10 mg/kg BW flutamide. Treatment with 25 mg/kg BW flutamide following trauma-hemorrhage, however, resulted in levels of cytokine release which were comparable with those found in sham-operated animals. No significant alterations in plasma corticosterone and testosterone levels were observed in any of the experimental groups. These findings indicate that short-term therapy of males with the androgen receptor blocker, flutamide at 25 mg/kg BW, following trauma-hemorrhage has protective effects on immune functions. This protective effect is dose dependent, since 10 mg/kg BW flutamide did not produce significant salutary effects. Thus, flutamide represents a novel and safe agent for improving the depressed functions in male trauma patients suffering severe blood loss.
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PMID:Flutamide: a novel agent for restoring the depressed cell-mediated immunity following soft-tissue trauma and hemorrhagic shock. 932 24

Escape from immune surveillance is critical for tumor progression in metastatic melanoma. We assessed the function of melanoma-derived dendritic cells (DCs) in patients presenting simultaneously with responding (rM) or progressing (pM) melanoma metastases. These rare coincidences allowed us to compare syngeneically the function of tumor DCs. CD83+ DCs were purified freshly from large responding (rDCs) or progressing (pDCs) metastases following chemoimmunotherapy. rDCs were 5 times more potent inducers of allogeneic T-cell proliferation than the pDCs that were used as control. Phenotypic analysis showed a marked depression of CD86 expression on pDCs. Culture supernatants from pM showed production of Th2-type cytokines [interleukin-10 (IL-10)], whereas a Th1 pattern [IL-2, interferon-gamma (IFN-gamma), IL-12) predominated in rM. The IL-10 detected in progressing metastases was directly derived from melanoma cells. Culture supernatants from metastases applied to DC-supported allo-MLR assays suppressed T-cell responses by 50-75% in the case of pM, but not rM. Finally, in a co-stimulation-dependent anti-CD3 tolerance assay, pDCs (but not rDCs) induced anergy in syngeneic CD4+ T cells. Anergy could be overcome by addition of IL-12 or IL-2. Our results show that melanoma-derived factors convert DC-antigen presenting cell function to tolerance induction against tumor tissue, changing tumor DCs to "silencers" of anti-tumoral immune responses.
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PMID:Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. 935 74


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