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)

Depression of cell-mediated immunity in patients following severe traumatic injury has been well documented in vitro and in vivo. However, the exact mechanism of this defect is still controversial. In this study, we have investigated the ability of injured patients' peripheral blood mononuclear cells (PBMC) to produce two important immunoregulatory molecules, interleukin 1 (IL 1) and interleukin 2 (IL 2). Eighteen traumatic injury patients were studied during the course of their hospital stay and their results compared with a group of 18 normal age- and sex-matched controls. The results showed the following. (1) Production of IL 2 by normal PBMC in response to optimal doses of mitogen may vary with sex as well as age. (2) Adherent mononuclear cells from trauma patients produced at least as much IL 1 as normals. (3) IL 2 production, however, was markedly suppressed (normals, 1.6 +/- 0.2 U; traumatic injury, 0.6 +/- 0.1 U; P = 0.001) and persisted for as long as 50 days postinjury. OKT4+ cells were not significantly decreased at any time, nor were OKT8+ suppressor/cytotoxic cells increased at any time. Decreased IL 2 production in patients treated with steroids or those who were septic was not different from that in those patients who were not treated with steroids or were not septic. These results suggest that the cause of the defect in IL 2 production in traumatic injury patients is not related to a lack of the IL 1 signal, producer T cells, or Ia+ monocytes or to increased suppressor T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of immunosuppression associated with severe nonthermal traumatic injuries in man: production of interleukin 1 and 2. 348 2

The mechanism(s) of stress-induced hypoferremia and hypozincemia remains unclear. We studied the role of granulocytes and lactoferrin (LF) in endotoxin and murine interleukin 1 (IL-1)-induced depression of serum Fe and Zn concentrations in both rabbits and rats. Both endotoxin and IL-1 administration induced significant hypoferremia (P less than 0.01) and hypozincemia (P less than 0.01) after 6 h in both species. Granulocyte depletion before IL-1 infusion significantly (P less than 0.01) diminished the hypoferremia but not the hypozincemia. Moreover, infusion of 5 or 15 mg of human LF into rabbits caused significant hypoferremia (P less than 0.005) without hypozincemia. Significant hypozincemia (P less than 0.01) could only be demonstrated after a 75-mg infusion. In contrast, infusions of human transferrin at equivalent doses (5, 15, and 75 mg) induced neither hypoferremia nor hypozincemia. Therefore endotoxin and IL-1-induced hypoferremia and, to a much lesser degree, hypozincemia are granulocyte dependent. Granulocyte released LF is a specific carrier molecule for transport and removal of Fe from the circulation during the acute phase response. The data suggest a mechanistic dissociation of IL-1-induced hypoferremia and hypozincemia with LF-independent mechanisms for Zn.
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PMID:Interleukin 1-induced depression of iron and zinc: role of granulocytes and lactoferrin. 349 23

C57BL/6 (susceptible) and A/J (resistant) mice were infected intravenously with a temperature-sensitive mutant of Salmonella typhimurium. In C57BL/6 mice a marked depression of the proliferative response of spleen cells to B and T mitogens occurred and was maximal at 2-3 weeks post-infection, whereas only minor changes were found in A/J mice. This immunodepression was mediated, at least in part, by adherent cells. Moreover, spleen cells from infected C57BL/6 mice did not produce interleukin-2 (IL-2) after concanavalin A stimulation. The impairment of IL-2 production was not related to a defect in IL-1 release. The addition of IL-2 to spleen cells did not restore their ability to respond to mitogens. The depression of mitogenic responses in infected C57BL/6 mice occurred at a time when increased resistance was present.
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PMID:Impairment of lymphocyte proliferative responses and interleukin-2 production in susceptible (C57BL/6) mice infected with Salmonella typhimurium. 351 42

The effects of low-dose single and continuous whole-body irradiation on immune functions were studied in C57BL/6 mice. Plaque-forming cell reaction of the spleen was found to be stimulated by single doses of x rays in the range of 0.025 to 0.075 Gy and by continuous exposure to gamma rays with a cumulative dose of 0.065 Gy. The reactivity of thymocytes to interleukin 1 showed a dose-dependent depression in the dose range of 0.025 to 0.25 Gy, but there was an increase in cell number in the thymus between doses of 0.025 and 0.10 Gy, resulting in enhancement of reaction of the whole organ. Unscheduled DNA synthesis of spleen cells was stimulated by single irradiation with 0.05 Gy and continuous irradiation with a cumulative dose of 0.13 Gy. The implications of these immunologic changes under low-dose radiation are discussed.
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PMID:Radiation hormesis: its expression in the immune system. 355 78

Recent studies have provided evidence that deficient interleukin-2 (IL-2) production by helper T cells contributes to the impaired T-cell-mediated functions observed in aged mice. Since most of these responses depend upon the presence of macrophages, a deficit in the functional capacity or in cell cooperation of macrophages may result in a decrease in immune reactivity. We found in the present study, that in vitro the cytostatic activity of macrophages from aged C57BL/6 (B6) mice is affected only slightly, but that in vivo their number increases with age. The synthesis of IL-1 is reduced when macrophages from aged mice are stimulated in vitro by lipopolysaccharide, but addition of exogenous IL-1 apparently does not restore either the mixed lymphocyte reaction or cytotoxic T lymphocyte generation. Co-cultures of young splenic macrophages with aged T lymphocytes do not restore to normal level the impaired proliferative response to T mitogens of aged B6 mice, but aged splenic macrophages provide a full accessory help for mitogenesis of young T cells. Thus, absorption of IL-1 by phytohemagglutinin-activated T cells is slightly altered in aged mice. IL-2 responsive T cells are not altered since exogenous IL-2 supply in vitro completely reconstitutes cytotoxic T lymphocyte generation after an allogeneic stimulation. Moreover, the number of Lyt 1+ cells is not modified in aged B6 mice. These results suggest that the impaired capacity of macrophages to release IL-1 and of blast T cells to bind IL-1 may contribute to the depression of cell-mediated immune reactivity associated with aging but also that the main defect is a functional lesion of IL-2 production by Lyt 1+ helper T cells.
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PMID:Interleukin-1 synthesis and activity in aged mice. 623 33

The aim of the present study was to characterize leukocytes present in a local inflammatory reaction with respect to production of prostaglandin E (PGE) and the release of factors affecting lymphocyte function, which are produced by macrophages (interleukin-1) or stimulated lymphocytes (interleukin-2). Lewis rats immunized against bovine serum albumin (BSA) were challenged by intraperitoneal injection of antigen. The PGE release by peritoneal cells (PEC) was tested in vitro and found to be enhanced in immunized rats before BSA challenge. However, PEC harvested after the injection of antigen showed a marked reduction in prostaglandin production during the first 24 hr. When these cells were tested for the secretion of lymphokines (IL-1, IL-2) the same depression was found.
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PMID:Depressed mediator release by inflammatory exudate cells in immunized rats following antigen challenge. 680 39

There is some evidence that major depression is characterized by systemic immune activation with involvement of phagocytic cells, T cell activation, B cell proliferation and increased autoantibody production. This paper reviews that major depression may be accompanied by higher concentrations of positive and lower concentrations of negative acute phase proteins (APPs). The most prominent abnormalities of APPs in major depression are increased haptoglobin (Hp) plasma levels. The latter are significantly and positively correlated with interleukin (IL)-6 production, various indices of systemic immune activation (e.g. monocytosis, neutrophilia, T cell activation) and with the vegetative symptoms of depression (e.g. anorexia, weight loss, psychomotor retardation, sleep disorders, anergy). Major depression is characterized by an altered distribution of Hp phenotypes and genes suggesting that genetic variation on chromosome 16 may be associated with this illness. It is concluded that increased production of IL-6 and IL-1 in major depression may underlie both immune activation and the "acute" phase response in that illness, and that disorders in Hp may be related to the pathophysiology and pathogenesis of major depression.
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PMID:A review on the acute phase response in major depression. 750 8

We and others have proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. An effect of NO on cardiac sarcolemmal L-type calcium channels has also recently been proposed. The spontaneous beating rate of neonatal cardiac myocytes is regulated by the sarcolemmal L-type calcium channel. Accordingly, we sought to determine if cytokine-stimulated NO production could also regulate beating rates of neonatal cardiac myocytes. Treatment of neonatal rat cardiac myocytes with TNF, IL-1, IL-6, 10(-5)M NMA, or 10(-3)M NMA significantly enhanced spontaneous beating rates compared to untreated myocytes in serum-free media for 48 hours (p < or = .01; n = 12 for each). Only IL-1 treatment resulted in significant nitrite levels vs. control over 48 hours (4.2 +/- 0.7 vs. 0.3 +/- 0.2 nmoles/1.25 x 10(-5) cells, respectively) (n = 12). Nitrite production by IL-1 was inhibited by 10(-3)M NMA but not 10(-5)M NMA (0.3 +/- 0.2 vs. 4.1 +/- 0.6 nmoles; p < .01; n = 12). The addition of 10(-5)M NMA to TNF, IL-1, and IL-6 did not alter the effect of the cytokines on the spontaneous beating rates of the cardiac cells (p < or = .01; n = 12 for each). These results strongly suggest that cytokines and NMA affect cardiac myocyte spontaneous beating rates through mechanisms independent of NO.
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PMID:Chronotropic effects of cytokines and the nitric oxide synthase inhibitor, L-NMMA, on cardiac myocytes. 752 6

In an attempt to understand better the immunoregulatory disorders in paracoccidioidomycosis (PCM), the possible correlation between interleukin pattern, lymphoproliferation, C-reactive protein (CRP) and specific antibody levels was investigated in the polarized clinical forms of this disease. We studied 16 PCM patients, eight with the disseminated disease (four under treatment and four non-treated) and eight with the chronic disease. The patients with disseminated disease exhibited high antibody titres specific to Paracoccidioides brasiliensis antigen compared with patients with the chronic form of disease. Tumour necrosis factor (TNF), IL-1, IL-6 and CRP in the serum of non-treated disseminated PCM patients were increased, which correlated positively with the low mitogenic response of peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA) (P < 0.01) and with the high antibody titres (P < 0.001) of these patients. Moreover, we found in the disseminated PCM patients positive correlations between IL-1 and IL-6 (P = 0.0007); IL-1 and TNF (P = 0.0045); IL-1 and IL-6 with the high antibody titres (P = 0.0834 and P = 0.0631, respectively); IL-1, IL-6 and TNF with CRP levels. By contrast, no correlations were found with those interleukins in the treated disseminated and chronic patients or in controls. It was interesting to find an inverse correlation between IL-4 and antibody production in non-treated disseminated PCM (r = -0.4770); moreover, a significant correlation (P = 0.0820) was found in chronic PCM patients with respect to the low level of either IL-4 and antibody titres against fungus antigen. Chronic PCM patients also had IL-2 levels inversely correlated with antibody production (r = -0.6313; P = 0.0628). Inverse correlations were also observed between IL-2 and IL-6 levels in non-treated disseminated patients (P = 0.0501) and between IL-2 and IL-4 in chronic patients (P = 0.0131). The inflammatory cytokines might have a pivotal role in the genesis and in control of some aspects of the disease, such as granulomatous reaction, hypergammaglobulinaemia and depression of T cell-mediated immunity in PCM.
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PMID:Differential correlation between interleukin patterns in disseminated and chronic human paracoccidioidomycosis. 764 15

We have previously proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. NO previously has been found to inhibit mitochondrial activity in other cell types. Accordingly, we sought to determine if cytokine-stimulated NO production inhibited cardiac myocyte mitochondrial activity. Treatment of neonatal rat cardiac myocytes with interleukin-beta (IL-1) resulted in the expression of mRNA for inducible NO synthase (iNOS) and stained positively for iNOS protein by immunohistochemistry. No iNOS staining was detected in untreated cells. IL-1 treatment resulted in significant nitrite levels vs control over 48 hrs (4.2 +/- 0.7 vs 0.3 +/- 0.2 nmol/1.25 x 10(5) cells, respectively) (n = 12) that was inhibited by 1mM NMA (0.3 +/- 0.2 nmoles; p < .01; n = 12). Mitochondrial activity was assessed by the MTT colorimetric assay using (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and OD 570-630. Mitochondrial activity was significantly inhibited by IL-1 vs control cells (0.436 +/- 0.01 vs 0.608 +/- 0.03) and reversed by 1mM NMA (0.549 +/- 0.03) or removal of IL-1 (0.662 +/- 0.02) (p < .01; n = 12 for each). These data strongly suggest that cytokine-stimulated NO production by cardiac myocytes results in reversible inhibition of mitochondrial activity.
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PMID:Cytokine-stimulated nitric oxide production inhibits mitochondrial activity in cardiac myocytes. 765 17


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