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

Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by the addition of gamma-irradiated autologous convalescent or allogeneic PBMC. Cell contact with the irradiated PBMC was necessary to restore proliferation. Non-T cells from the acute PBMC of dengue patients did not support proliferation of T cells from control donors in response to PHA, but T cells from the PBMC of patients with acute dengue proliferated if accessory cells from a control donor were present. Addition of anti-CD28 Abs restored anti-CD3-induced proliferation of the PBMC of some patients. The percentage of monocytes was reduced in the acute sample of PBMC of the dengue patients. Addition of IL-2 or IL-7, but not IL-4 or IL-12, also restored proliferation of acute PBMC stimulated with anti-CD3. The results demonstrate that both quantitative and qualitative defects in the accessory cell population during acute dengue illness result in a depression of in vitro T cell proliferation.
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PMID:Impaired T cell proliferation in acute dengue infection. 1022 44

A number of studies documented that the heavy metals are not only toxic for the organisms but they may modulate immune responses. The immunomodulatory activity was proved in several in vivo and in vitro model systems. In the current study, immunomodulatory activities of lead and cadmium are presented. The viability of both lymphocytes and macrophages was affected by heavy metals in a dose- and time-dependent manner. In the case of lead, the depression of N-oxide production closely correlated with increased blast transformation of spleen cells induced by concanavalin A (ConA). On the contrary, cadmium suppressed the production of N-oxides but stimulated significantly the proliferation of spleen cells. The production of cytokines by lymphocytes and macrophages was dependent on the in vitro model used. Generally, the treatment of macrophages with lead results in disregulation of the production of proinflammatory cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 1alpha (IL-1alpha) and interleukin 6 (IL-6)] and preferential production of Th1 type of cytokines (IFN-gamma and IL-2). Cadmium seemed to trigger the Th2 cytokine regulatory pathway [interleukin 4 (IL-4), interleukin 10 (IL-10)]. The results suggest the metal-induced changes in immunoregulatory mechanism of host with potentially severe clinical consequences.
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PMID:The immunomodulatory effect(s) of lead and cadmium on the cells of immune system in vitro. 1069 59

T cells implicated in chronic inflammatory diseases such as RA respond weakly when stimulated in vitro with mitogen or antigen. The mechanism behind this hyporesponsiveness is unclear, but a depressed expression of the T cell receptor (TCR)-associated CD3zeta chain has been suggested. In the present work we describe a low expression of CD3zeta in synovial fluid (SF) T cells from RA patients compared with peripheral blood (PB) T cells, but no difference in CD3zeta expression between RA and healthy control PB T cells. In vitro studies demonstrated that granulocytes but not SF macrophages are able to down-regulate the expression of CD3zeta. Through stimulation with anti-CD3 antibodies we demonstrated that the TCR-dependent proliferative response was decreased in SF T cells compared with PB T cells. Stimulation with phorbol ester and ionomycin also resulted in a low proliferative response of SF T cells, indicating that both signal transduction through the TCR (stimulation with anti-CD3) and events further downstream in the signalling pathways (stimulation with phorbol ester and ionomycin) are affected. A similar depression of T cell activity was observed when induction of IL-2 and IL-4 was measured. However, SF T cells were not defective in the induction of interferon-gamma (IFN-gamma) when stimulated with phorbol myristate acetate (PMA)/ionomycin, in contrast to the diminished IFN-gamma response observed after stimulation with anti-CD3. This indicates that the hyporesponsiveness of SF T cells can not be generalized to all T cell functions. The differential response to external stimuli is likely to be of importance for the capacity of SF T cells to influence inflammatory reactions.
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PMID:Down-regulation of the T cell receptor CD3 zeta chain in rheumatoid arthritis (RA) and its influence on T cell responsiveness. 1075 80

The purpose of this study was to evaluate the potential efficacy of alternating two outpatient regimens for the treatment of metastatic renal cell cancer. These regimens consisted of 4 weeks of recombinant interleukin 2 (rIL-2) plus IFN-alpha2B followed by 4 weeks of 5-fluorouracil plus IFN-alpha2B. Fifty patients meeting eligibility criteria of previous Cytokine Working Group studies were treated on an outpatient basis. Patients received s.c. rIL-2 (Proleukin; Chiron, Emeryville, CA) during weeks 1-4 of the 8-week regimen. During weeks 1 and 4, the dosage for rIL-2 was 10 MIU/m2 twice daily on days 3-5, and the dosage for IFN-alpha2B (Intron; Schering Plough, Kenilworth, NJ) was 6 MIU/m2 on day 1. During weeks 2 and 3, the dosage for rIL-2 was 5 MIU/m2 on days 1, 3, and 5, and the dosage for IFN-alpha2B was 6 MIU/m2 on days 1, 3, 5. During weeks 5-8, 5-fluorouracil (750 mg/m2) was administered once weekly by i.v. infusion, and IFN-alpha2B (9 MIU/mZ) was administered as a s.c. injection three times weekly. Throughout the treatment, an assessment of quality of life was made and a symptom-distress scale was evaluated. There were two patients with complete responses (CRs) and seven with partial responses (PRs) for an objective response rate of 18% (95% confidence interval, 10-25). The median response duration was 8 months (range, 3-51+ months). The CRs lasted 5 months and 51+ months and the PRs ranged from 3+ to 18 months. After completing at least one course of treatment, eight patients (three with PR, one with minor response, four with stable disease) became CRs after surgery for remaining metastatic disease. Six remain alive at 43+ to 53+ months, and 5 remain disease-free since surgery. The median survival of the study group is 17.5 months, with a maximal follow-up of 53+ months. The range in survival is 1-53+ months. Toxicity was primarily constitutional. and treatment modifications were designed to maintain toxicity at grade 2/3. The most common toxicities during treatment with IL-2/IFN were fatigue, nausea/vomiting, anorexia, skin reaction, diarrhea, fever, and liver enzyme elevations. One-third had central nervous system toxicity (headache, depression, insomnia). During 5FU/IFN treatment, 49 of 50 patients experienced grade 2/3 myelosuppression during course 1. Eight patients experienced grade 4 toxicities. In conclusion, the activity of this alternating regimen is similar to that of IL-2/IFN alone, given in 4-week cycles. The addition of 5FU/IFN failed to increase the efficacy and added new toxicity (myelosuppression). This report does not confirm the results previously reported for either alternating or simultaneous administration of these three agents. Because 5FU does not appear to add to the antitumor activity of IL-2-based therapy for renal cancer, current efforts are directed toward a Phase III randomized comparison of high-dose i.v. bolus inpatient IL-2 treatment versus treatment with outpatient s.c. injection of IL-2 plus IFN.
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PMID:Phase II trial of interleukin 2, interferon alpha, and 5-fluorouracil in metastatic renal cell cancer: a cytokine working group study. 1099 27

Recent experimental studies have found gender differences in the immune response after hemorrhagic shock with an enhanced immune function and lower mortality after subsequent sepsis in females than in males. Interleukin-10 (IL-10) has been shown to play a potential role in the treatment of early proinflammatory state after hemorrhagic shock. Although studies showed beneficial effects of the treatment with IL-10, it remains unclear whether the effects are gender related. To study this, male and female CBA/J mice were subjected to hemorrhage (35+/-5 mmHg for 90 min and fluid resuscitation) or sham operation. At resuscitation, each received either recombinant murine IL-10 (rmIL-10) or placebo i.p. At 48 h after resuscitation, peritoneal macrophages (pMphi) and splenocytes were harvested. IL-1beta and IL-12 release by pMphi and splenocyte proliferation and splenocyte IL-2 and interferon (IFN)-gamma release capacity were assessed. Interleukin-10 plasma levels were not increased after rmIL-10 treatment. The results indicate that rmIL-10 treatment restores depressed immune response (splenocyte proliferation, IFN-gamma, IL-1beta in males after hemorrhagic shock. In contrast, the immune responses after shock in females were not influenced by rmIL-10, with the exception of depressed splenocyte proliferation. In addition, sham-operated male mice treated with rmIL-10 showed immune depression compared with the placebo group. Thus, administration of rmIL-10 during resuscitation after hemorrhage produces salutary effects on the depressed immune responses in males but did not further enhance the immune functions in females under those conditions.
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PMID:Gender-related therapy: early IL-10 administration after hemorrhage restores immune function in males but not in females. 1102 56

The authors assessed the impact of osteopathic manipulative treatment (OMT) as an adjunct to standard psychiatric treatment of women with depression. Premenopausal women with newly diagnosed depression were randomly assigned to either control (osteopathic structural examination only; n = 9) or treatment group (OMT; n = 8). Both groups received conventional therapy consisting of the antidepressant paroxetine (Paxil) hydrochloride plus weekly psychotherapy for 8 weeks. Attending psychiatrists and psychologists were blinded to group assignments. No significant differences existed between groups for age or severity of disease. After 8 weeks, 100% of the OMT treatment group and 33% of the control group tested normal by psychometric evaluation. No significant differences or trends were observed between groups in levels of cytokine production (IL-1, IL-10, IL-2, IL-4, and IL-6) or in levels of anti-HSV-1, anti-HSV-2, and anti-EBV antibody. There was no pattern to the osteopathic manipulative structural dysfunctions recorded. The findings of this pilot study indicate that OMT may be a useful adjunctive treatment for alleviating depression in women.
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PMID:Adjunctive osteopathic manipulative treatment in women with depression: a pilot study. 1157 38

The relationship between immune activation and the development of early depressive symptoms were studied in 33 cancer patients undergoing cytokine therapy. Patients were treated either with subcutaneous IL-2 administered alone (n=13) or in association with IFN-alpha (n=5), or with IFN-alpha alone administered subcutaneously at low doses (n=5) or intravenously at high doses (n=10). The intensity of depressive symptoms was assessed during a clinical interview carried out before the start of cytokine therapy and five days later using the Montgomery and Asberg Depression Rating Scale (MADRS). On the same days, blood samples were collected for each patient to measure serum concentrations of cytokines (IL-6, IL-10, IL-1ra) and cytokine-receptors (sIL-2R, LIF-R). Results showed that patients treated with IL-2 or IL-2+IFN-alpha displayed concomitant mood symptoms and increased serum cytokine levels during treatment. In these patients, the intensity of depressive symptoms at endpoint was positively correlated with the increases measured in serum levels of IL-10 between baseline and endpoint. IL-10 is an anti-inflammatory cytokine that is produced in response to the production of pro-inflammatory cytokines, and thereby reflects an inflammatory response. These results support the hypothesis of close relationship between depressive symptoms and the activation of the cytokine network.
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PMID:Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy. 1158 80

Interleukin level and mononuclear phagocytes (MPh) activity have been studied in 19 patients with mono- and bipolar depression. All the patients were examined at admission to a hospital before treatment. The depression was characterized by low MPh activity, a significant (p < 0.05) fall in IL-1 beta production by stimulated monocytes, a trend to reduction of IL-2 production by stimulated lymphocytes, significant (p < 0.05) IL-2 serum concentration increase and significant (p = 0.05) decrease of soluble IL-2 receptor (siL-2R) concentration in the serum. Significant positive correlation (r = 0.76; p < 0.05) between MPh activity and IL-1 beta production has been found. Interleukin alterations were most manifest at the early disease stage (symptoms onset is less than one year). It is suggested that IL-2 accumulation in the blood serum in these patients is strongly influenced by a significant decrease of siL-2R serum concentration. MPh (the main IL-2 producers) activity reduction results in the monocyte IL-1 beta production decrease followed by changes in interleukin (in particular, IL-2) production by lymphocytes and other changes in interleukin system.
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PMID:[Interleukin level in endogenous depression]. 1158 4

The object of the study was to determine whether male and female sex steroids produce divergent effects on Th1 and Th2 cytokine release following trauma-haemorrhage. Recent studies indicate that androgens are responsible for the depressed splenocyte Th1 cytokine release in males following trauma-haemorrhage. In contrast, female mice maintain their Th1 cytokine release capacity following trauma-haemorrhage. Nonetheless, the effect of male and female sex steroids on Th1 and Th2 cytokine release following trauma-haemorrhage remains unknown. Male C3H/HeN mice were castrated and treated with pellets containing either vehicle, 5alpha-dihydrotestosterone (DHT), 17beta-estradiol (estradiol), or a combination of both steroid hormones, for 14 days prior to soft-tissue trauma (i.e. laparotomy) and haemorrhagic shock (35+/-5 mmHg for 90 min followed by adequate fluid resuscitation) or sham operation. Untreated male and female mice, as well as DHT treated female mice, served as control groups. Twenty-four hours later the animals were sacrificed, plasma obtained and splenocytes harvested. Plasma DHT and estradiol levels in treated animals were comparable with intact male and female mice, respectively. A significant depression of splenocyte Th1 cytokines, i.e. IL-2, IFN-gamma, was observed in DHT treated castrated animals, DHT treated females, and untreated males following trauma-haemorrhage, as opposed to maintained Th1 cytokine release in estradiol treated and estradiol/DHT treated castrated animals and females. The release of the anti-inflammatory cytokine IL-10 was markedly increased in DHT treated mice and males subjected to trauma-haemorrhage compared to shams, but decreased in estrogen treated mice and females under such conditions. These results suggest that male and female sex steroids differentially affect the release of Th1 and Th2 cytokines following trauma-haemorrhage and should be further studied for their potential to modulate splenocyte function in trauma victims.
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PMID:Testosterone and estrogen differently effect Th1 and Th2 cytokine release following trauma-haemorrhage. 1166 83

Macrophages produced proinflammatory cytokines and inflammatory responses can cause many symptoms of depression, including direct stimulation of the HPA axis and secretion of cortisol. In depressed patients, hypercortisolism has been well described as one of the major symptoms and also as the cause for hippocampal atrophy and memory impairment. In this paper, the relationships between thymectomy, increased IL-1 levels, and changes in corticosterone and neurotransmitter concentrations in rats are discussed, as well as their implications for memory impairments and depression. In thymectomized rats, deficits in both spatial and fear conditioned memory have been observed. Thymectomy decreases noradrenaline and dopamine levels, and increases serotonergic neurotransmission in limbic areas, without affecting corticosterone concentrations. In a depression model, thymopeptides or IL-2 treatment significantly attenuated changes in behavior, lymphocyte proliferation and neurotransmitters caused by bulbectomy. The reduction of thymic functions may increase IL-1 synthesis. Central IL-1beta administration impairs rat's spatial memory in the Morris water maze and 8 arms radial maze, but enhances conditioned memory in the passive avoidance. These changes can be reversed by either IL-1 receptor antagonist or a glucocorticoid receptor antagonist (RU 486). Furthermore, IL-1-induced changes in some neurotransmitter systems are similar to those observed in thymectomized rats. However, both acute and sub-chronic IL-1 administration increases plasma corticosterone concentrations. Together, these findings suggest that changes in the function of the thymus gland may play an important role in the unbalance between macrophages, cytokines, and lymphocytes, which induces neurotransmitter and neuroendocrine changes, and memory disturbances in depressive illness.
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PMID:The effect of thymectomy and IL-1 on memory: implications for the relationship between immunity and depression. 1240 69


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