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)

The depression of interleukin-2 synthesis represents a major dysfunction within the cascade of immunologic defects induced by mechanical and thermal trauma. This study was undertaken to elucidate the negative control mechanisms that were responsible for the deficiency of IL-2 production in polytraumatized patients. Peripheral blood mononuclear cells (PBMC's) from 29 patients (average age, 35.8 years; average ISS, 35) were separated on post-trauma days 1, 3, 5, 7, 10, 14, and 21 and cultured as untreated cells (C), cells treated with indomethacin (C + INDO), and cells depleted of adherent cells (C-AC). Cell cultures were assayed for proliferative responses to PHA, IL-2 synthesis, PGE2 production, gamma-interferon levels, and phenotyping studies. On all days post-trauma there was found a marked reduction of IL-2 production compared to controls with a highly significant nadir from day 5 to day 10 with an almost 80% inhibition of IL-2 (p less than 0.005). C + INDO cells showed increases of IL-2 synthesis over untreated cells ranging from 48% (Day 1) to 220% (Day 7). Removal of adherent cells (C-AC) did not reverse the suppression of IL-2 production. gamma-interferon levels were depressed in parallel with IL-2 levels but did not increase with C + INDO. The phenotyping of the PBMC's showed highly significant suppression of OKT3+, OKT4+, and IL-2R+ lymphocytes as well as a highly significant elevation of the monocyte (p less than 0.005) count. There was a highly significant increase of PGE2 synthesis from monocytes, due to the monocytosis and to a higher capacity of synthesis of the individual cells following trauma. PGE2 levels peaked on Day 5 and 7 post-trauma at 400% of control (p less than 0.005). These data suggest that the suppression of IL-2 synthesis post trauma is caused mainly by two factors: the excessive PGE2 output of inhibitory monocytes and inadequate function in immature and/or blocked lymphocytes. The partial restoration of IL-2 synthesis by indomethacin suggests that blockade of the cyclo-oxygenase pathway as an immunomodulating therapy may reverse some of the immunologic abnormalities in multiple trauma patients.
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PMID:Prostaglandin E2 (PGE2)-dependent suppression of interleukin alpha (IL-2) production in patients with major trauma. 295 32

Mitogen (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMC) was reduced by more than 70% 2 h after the haemorrhage of 30% of blood volume. Experiments using isolated macrophages and lymphocytes showed that post-haemorrhage macrophages were functionally normal and that lymphocytes were responsible for the observed haemorrhage-induced depression of proliferative response. Surface marker determinations showed that at least some, if not all, of the haemorrhage-induced suppressor cells are of the OX8+ phenotype. Exposure of PBMCs to serum from bled animals also brought about activation of OX8+ suppressor T cells. These results suggest that the depressed proliferative response of PBMCs induced by haemorrhage or by exposing the cells to haemorrhagic serum (serum from bled animals) is due to the activation of OX8+ suppressor T cells.
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PMID:Generation of functionally active suppressor cells by haemorrhage and haemorrhagic serum. 297 Mar 52

A 54-year-old asymptomatic male patient was followed for more than 7 y and presented a constant T cell lymphocytosis without skin involvement or bone marrow depression. No clinical or haematological aggravation was noted during this follow-up. Morphologically, the cells were large granular lymphocytes strongly positive for beta-D-glucuronidase, negative for acid phosphatase and with features of T cells on transmission and scanning electron microscopy. The immunological studies of the lymphocytes showed the following parameters: E rosettes+, mouse rosettes-, SmIg-, OKT3+, OKT4+, OKT8-, OKT6-, Ia-, TdT-, NK-, HTLV-, decreased PHA and PWM stimulation, no interleukin 2 production and failure to enhance Ig synthesis in a PWM driven system. The karyotype was normal. This case of chronic T cell lymphocytosis with large granular lymphocytes helper profile and defect of helper function, not reported in the literature, may correspond to a distinct entity in the heterogeneous group of chronic T cell disorders.
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PMID:Chronic T cell lymphocytosis with large granular lymphocytes of helper (OKT4) phenotype. 298 13

The mechanism by which prostaglandin E2 (PGE2) inhibits human T lymphocyte activation and proliferation was studied. We analyzed the effect of physiologic concentrations of PGE2 on interleukin 2 (IL 2) production, expression of IL 2 receptor (Tac antigen), and expression of the transferrin receptor after in vitro activation with phytohemagglutinin. PGE2 inhibited T lymphocyte proliferation by 80 to 90% of control values. This was associated with a similar degree of inhibition of IL 2 production while the expression of IL 2 receptor was not affected. This was in marked contrast to the expression of the transferrin receptor, which was inhibited 65% after 72 hr of in vitro activation. The addition of exogenous, purified IL 2 reconstituted lymphocyte proliferation to 50% of control values, but had no effect on transferrin receptor expression. Because PGE2 is known to increase the intracellular concentration of 3',5' cyclic adenosine monophosphate (cAMP), we investigated the effect of another adenylate cyclase activator, i.e., isoproterenol, as well as the effect of extracellular administration of the cAMP derivative dibutyryl cAMP (dBcAMP) on IL 2 production, Tac antigen expression, and transferrin receptor expression. It was demonstrated that isoproterenol, as well as dBcAMP, inhibited transferrin receptor expression on PHA-activated T lymphocytes to the same extent as PGE2, and exogenous IL 2 could not counteract the down-regulation of the receptor expression. In contrast, neither isoproterenol nor dBcAMP had any significant effect on IL 2 receptor expression. Prostaglandin F2 alpha (PGF2 alpha), which has been reported to elevate intracellular cyclic GMP levels, had no effect on lymphocyte activation and proliferation, and did not counteract the PGE2-induced depression in IL 2 production. In contrast to its effect on peripheral blood lymphocytes, PGE2 had no effect on transferrin receptor expression or cell proliferation by IL 2-dependent T cell clones and IL 2-independent T cell lines. These studies demonstrate that PGE2 exerts its inhibitory effects on T cell activation and proliferation via two distinct pathways: inhibition of IL 2 production and inhibition of transferrin receptor expression. The transferrin receptor inhibition is mediated via the cAMP pathway and is IL 2-independent.
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PMID:Prostaglandin E2 acts at two distinct pathways of T lymphocyte activation: inhibition of interleukin 2 production and down-regulation of transferrin receptor expression. 298 62

Cellular immune reactivity was investigated in 49 newly diagnosed children with Wilms' tumor and compared to age-matched control. The level of total T (T4 degrees) and B lymphocytes was normal while the relative number of T lymphocytes with high affinity receptors for sheep erythrocytes (T29 degrees) was significantly decreased in the patients studied. The lymphocyte response to PHA in vitro was diminished but PHA-induced lymphokine production was not altered. The depression of T29 degrees level and lymphocyte reactivity to PHA was associated with high grade tumor rather than with the clinical stage. Lymphocytes of 42-47% patients reacted with autochthonous and allogeneic KCl tumor extracts in the migration inhibition test and the degree of reactivity was related to the histological differentiation of the tumor.
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PMID:Immunological reactivity in children with Wilms' tumor. 302 Apr 56

Beta-endorphin (10(-11)-10(-9) M) has been shown to induce naloxone-independent depression of the proliferative activity of human peripheral lymphocytes (HL), stimulated by pokeweed mitogen without affecting PHA-stimulated HL proliferation. Beta-endorphin (10(-10)-10(-7) M) also caused changes in HL cAMP level, that were blocked by naloxone. Marked individual sensitivity to beta-endorphin effects has been noted. It has been also shown that a bone marrow preparation, stimulating antibody production (myelopeptides), causes naloxone-independent depression in the proliferative activity of HL, stimulated by PHA and pokeweed mitogen, as well as naloxone-blocked decrease in cAMP HL level. It has been concluded that beta-endorphin interacts with several types of opiate lymphocyte receptors and that opioids, contained in myelopeptides, are involved in the realization of myelopeptide effect on lymphocytes.
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PMID:[Effect of beta-endorphin and myelopeptides on the cAMP level and proliferation of lymphocytes in vitro]. 302 14

The cytogenetic effects of methyl acetimidate (MAI), a lysine-specific protein crosslinking reagent, were investigated using human peripheral lymphocytes in culture. Lymphocytes were treated with the chemical either prior to PHA exposure or 2-3 days following mitogenic stimulation and assessed for perturbations in cellular proliferation and induction of SCEs. Severe reductions in the mitotic index (MI) and pronounced decreases in the proportion of metaphases proceeding beyond M(1) were observed following G0 exposure to MAI concentrations of as low as 2 mM; with complete suppression of mitotic activity in all cultures exposed to levels of 3 mM MAI or greater. Concentrations resulting in severe depression in MI caused only moderate increases in SCEs. Cells exposed to less than 10 mM MAI during the late S-G2 stages of the cell cycle and harvested at the first metaphase following treatment exhibited profound mitotic delay, impaired prophase to metaphase transitions and abnormal mitotic configurations. These findings demonstrate that protein-specific crosslinking agents may induce a wide spectrum of adverse cytogenetic outcomes in both cycling and noncycling lymphocytes.
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PMID:Cytogenetic evaluations in human lymphocytes exposed to methyl acetimidate, a lysine-specific protein crosslinking agent. 311 24

Previous studies in our laboratory have indicated that in utero chlordane exposure caused a significant enhancement in the survival of the offspring to influenza virus infection. Further studies, reported here, show that the non-specific delayed type hypersensitivity (DTH) response to oxazolone at 100 days of age, but not at 30 days of age, was significantly depressed. In contrast, the Con A-induced blastogenic response of spleen cells from chlordane-treated offspring was not depressed and was, in fact, significantly enhanced. However, neither the response to PHA nor to LPS mitogens was significantly altered. In utero exposure to chlordane significantly depressed the mixed lymphocyte reactivity (MLR) of spleen cells from male offspring, whereas females showed no significant alteration of MLR. The significant depression of the DTH and MLR responses supports our previous reports of enhanced survival of influenza virus infection following in utero exposure to chlordane, since active DTH contributes to the pathology of influenza virus infection in mice. The normal or enhanced T-cell mitogen response suggested that the chlordane-induced depression of DTH and MLR was not due to overt toxicity to T-cells.
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PMID:The effect of prenatal chlordane exposure on the delayed hypersensitivity response of BALB/c mice. 315 28

Beta-2-adrenergic agonists are often employed in the treatment of acute bronchostenosis. Following our recent investigations into the influence of some drugs (cromolyn, ketotifen, theophylline) on the immune response, in this study we analyzed the in vitro effects of fenoterol (beta-2-adrenergic agonist) on the immune response. The mitogen-(PHA)-induced proliferation of peripheral mononuclear cells (PMNC), the PMNC proliferation induced by anti-T3 and anti-T11 monoclonal antibodies (MAbs), the PHA-induced lymphokine--interleukin 2 (IL-2) and interferon-gamma (IFN-gamma)--production were studied in ten healthy volunteers. Since the plasmatic peak of fenoterol following a single inhalation of 200 micrograms is about 20 ng/ml, in the experiments herein reported the drug was tested in the cultures at concentrations lower, equal and higher than the plasmatic peak: respectively, 2, 20 and 200 ng/ml. Furthermore, for a more detailed study of T-lymphocyte activities, we also evaluated the effect of fenoterol on T-cell clone proliferation. Our results, which reveal no effects of fenoterol on the studied immunological parameters, acquire relevance when related to our previous reports showing a depression of the immunological response exerted by theophylline and ketotifen.
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PMID:Fenoterol effects on the in vitro immune response. 317 57

We studied the effect of vitamin B complex (vitamin B1, B6 and B12 complex) on the immune responsiveness in gastric cancer patients who underwent surgery. The depression of blastogenic responses to both PHA and PWM was observed 2 weeks after surgery in half of the patients treated with Vitamedin but the degree was significantly less than that in the control patients without vitamin B treatment whose lymphocyte responses were depressed. Moreover, the blastogenic responses were induced by vitamin B administration 2 or 4 weeks after surgery in 5 of the 8 stage III-IV patients whose lymphocytes had not responded prior to surgery. Four weeks after surgery, the patients without vitamin B treatment showed only a tendency of recovery of their lymphocyte responses, whereas the recovery of blastogenic responses in the patients treated with vitamin B was significant. Essentially similar results were obtained with skin reactions to PHA and PPD. These results suggest that the administration of vitamin B1, B6 and B12 complex is useful for the protection against and the recovery of immune dysfunction produced by surgery in cancer patients.
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PMID:Effect of vitamin B complex on the immunodeficiency produced by surgery of gastric cancer patients. 321 Mar 44


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