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)

Although studies indicate that simple hemorrhage induces profound depression of cell-mediated immunity and enhances the host's susceptibility to sepsis, the mechanism for this remains unknown. Since the Kupffer cells (KC) are positioned to have constant exposure to various immunomodulators and antigens released during hypotension, we have examined whether antigen presentation by KC, a critical component in eliciting an antigen specific immune response or those processes associated with it, are depressed following hemorrhage. C3H/HeN mice were bled to and maintained at a mean BP of 35 mmHg for 60 min, and then resuscitated with their own blood and adequate fluids. The mice were killed at varying periods of time after hemorrhage to obtain KC from the liver, and assessed for their capacity to present antigen to a sensitized clone Th/cell line (D10.G4.1). Hemorrhaged mice exhibited a marked decrease in antigen presenting capacity beginning as little as 2 h and lasting up to 3-5 days post-hemorrhage. The ability of KC to express mouse interleukin 1 (mIL-1) showed a significant decline at 2 h following hemorrhage, but this effect was not apparent at 24 h post-hemorrhage. In contrast, KC capacity to produce IL-1, IL-6 and tumour necrosis factor (TNF) (cytokines which can co-stimulate T cell antigen presentation) was markedly enhanced during the first 24 h following hemorrhage. A marked decrease was observed in both the mean of the average fluorescence per KC and the percent of Ia antigen-positive KC which persisted for at least 3 days after hemorrhage. The ability of ibuprofen (a cyclooxygenase blocker) to partially restore the antigen presenting capacity of KC from hemorrhaged mice in vitro indicates that prostaglandins are involved in this dysfunction. Thus, the depression of KC antigen presentation, as well as the enhanced capacity of these cells to release inflammatory mediators (TNF, IL-1, IL-6 and prostanoids) which may produce cell and organ dysfunction, could contribute to the host's enhanced susceptibility to sepsis following hemorrhage.
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PMID:Differential effects of hemorrhage on Kupffer cells: decreased antigen presentation despite increased inflammatory cytokine (IL-1, IL-6 and TNF) release. 131 64

A preparation of a triacontanol-containing compound was studied for its effect on cells involved in the inflammatory response. C57BL/6 mice were injected intraperitoneally with various concentrations of this compound and investigated for total body weight, wet weight of thymus tissue, number of thymus cells and splenocytes, interleukin 1 production of spleen monocytes, and response of splenocytes to the T cell mitogen, phytohemagglutinin. Mice treated with the triacontanol preparation exhibited decreased total body weight, 24% reduction in thymus weights, 39% decrease in the number of thymus cells, and 21% depression in total splenocytes. Splenic monocytes of these animals produced a significantly reduced amount of interleukin 1 and splenocytes had a significantly depressed response to phytohemagglutinin. It is concluded that triacontanol has an inhibitory effect on at least some of the cells responsible for inflammation.
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PMID:Effect of triacontanol on numbers and functions of cells involved in inflammatory responses. 161 10

The effects of all-trans-retinoic acid were investigated on the immune responses in C57Bl/6 mice after daily oral administration for one week. In selected experiments the immunosuppressive chemicals, cyclophosphamide and cyclosporin A were used in conjunction with retinoic acid. Retinoic acid stimulated the production of antibodies against sheep red blood cells and DNP-Ficoll; however, retinoic acid did not reverse the depression caused by immunosuppressive chemicals. In non-immunized animals retinoic acid stimulated the production of IL-1 but not of IL-2. The mitogenic responses of splenocytes against concanavalin A, phytohemagglutinin and pokeweed mitogen were depressed after the retinoic acid treatment; those against lipopolysaccharide were not influenced. Treatment with retinoic acid did not alter the mixed leukocyte responses but increased the activity of NK cells. Results indicate that retinoic acid may act as an adjuvant via activating macrophages, however, retinoic acid cannot reverse the immunosuppression induced by potent chemicals.
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PMID:Adjuvant activity of all-trans-retinoic acid in C57Bl/6 mice. 162 15

Studies indicate that simple hemorrhage produces a profound depression of cell-mediated immunity, thereby contributing to an enhanced susceptibility to septic challenge in the host. However, it remains unknown whether or not the macrophages' cytotoxic capacity is altered after hemorrhage. To study this, C3H/HeN mice were bled to and maintained at a blood pressure of 35 mm Hg for 60 min, and adequately resuscitated. Mice were then killed at 2 or 24 h after hemorrhage to obtain peritoneal macrophage, splenic macrophage, and Kupffer cells. Cytotoxicity was assessed by determining the capacity of these macrophages to lyse [3H]TdR labeled WEHI-164 clone 13 or P815 tumor target cells (WEHI-164, sensitive to both soluble and cell-associated TNF vs P815 cells, insensitive to soluble TNF). Peritoneal and splenic macrophages from hemorrhaged animals exhibited a significantly reduced cytotoxic capacity, whereas Kupffer cells' ability to kill the target cells was enhanced. Similarly, the Kupffer cells' capacity to release TNF and IL-1, as well as express cell-associated forms of this cytokine are significantly enhanced on macrophages isolated 2 h after hemorrhage, whereas peritoneal macrophages are not. Furthermore, antibodies directed at mouse TNF but not against murine IL-1 alpha or murine IL-6 were able to oblate the enhanced target cell lysis of unfixed, as well as paraformaldehyde fixed (metabolically inactive) Kupffer cells. Studies using inhibitors (GN-monomethyl-arginine, superoxide dismutase, catalase, and ibuprofen) of other TNF-inducible mechanisms of target cell killing indicated that only the inhibition of the release of reactive nitrogen consistently depressed the cytotoxic capacity of Kupffer cells from hemorrhaged mice. Thus, the increased Kupffer cell cytotoxicity from hemorrhaged mice is most likely mediated through the expression of cell-associated TNF and the release of reactive nitrogen.
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PMID:Hemorrhage induces enhanced Kupffer cell cytotoxicity while decreasing peritoneal or splenic macrophage capacity. Involvement of cell-associated tumor necrosis factor and reactive nitrogen. 175 90

We compared the early and late pulmonary effects of human recombinant tumor necrosis factor (TNF) and interleukin 1 (IL-1) challenges in awake dogs with chronic tracheostomies. Serial blood gas analysis, bronchoalveolar lavage (BAL) with cell and protein analysis, intravascular catheter hemodynamics, and radionuclide left ventricular ejection fractions (LVEF) were determined before and after infusion of TNF (60 micrograms/kg body wt, n = 8), IL-1 (1,000 micrograms/kg body wt, n = 6), or heat-inactivated IL-1 (n = 6, controls). Controls given heat-inactivated IL-1 had no changes (P = NS) in any pulmonary parameter throughout the study. Animals given IL-1 had a transient increase (P less than 0.05) in BAL neutrophil concentration 1 day after infusion but no other changes (P = NS) in pulmonary function throughout the study. Animals given TNF had early (0-4 h) decreases (P less than 0.05) in arterial PO2, increases (P less than 0.05) in physiological shunt fraction and alveolar-to-arterial PO2 gradient, and a high mortality rate (50%). In TNF animals, volume challenges at 4 h were associated (P less than 0.05) with death and noncardiogenic pulmonary edema. In TNF survivors, hypoxemia persisted for 2-3 days and was associated with increases (P less than 0.05) in alveolar protein and neutrophil concentration on days 1 and 3, respectively, which in survivors returned to near normal over 6-21 days. Animals challenged with TNF and not IL-1 had reversible depression of LVEF similar in time course to abnormalities in arterial PO2. In this study, TNF (but not IL-1) challenges were lethal and produced acute pulmonary dysfunction sustained over days (reversible in survivors) that was similar to that seen in human septic shock. The ability of TNF to induce pulmonary injury similar to bacterial shock suggests that TNF is a key mediator of sepsis-induced lung injury. Furthermore, because TNF challenge induced both sustained pulmonary and cardiac injury, TNF may be a common pathway for the multiple organ dysfunction that occurs during septic shock.
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PMID:TNF but not IL-1 in dogs causes lethal lung injury and multiple organ dysfunction similar to human sepsis. 176

The effects of human recombinant interleukin-1 beta (IL-1 beta) were investigated on recently isolated (1 to 3 weeks) and on well-established (older than 3 weeks) monolayer cultured human articular chondrocytes. IL-1 beta was found to depress 35S-proteoglycan synthesis rates and to enhance prostaglandin E2 (PGE2) production in these monolayer cultured chondrocytes. Induction of 35S-proteoglycan-degradative activity by these cells also occurred in IL-1 beta treated cultures. These "catabolin" -IL-1 activities were observed in recently isolated as well as in well-established "old" cultures. IL-1 beta increased 3H-thymidine incorporation rates in the "old" cultures. However, in recently isolated chondrocytes a dose-dependent reduction of the 3H-thymidine incorporation occurred. The depression of mitotic activity in these cells was partially abolished by indomethacin, indicating that this depression was a PGE2 effect. However, supplementing IL-1 beta with indomethacin did not raise the 3H-thymidine incorporation rates above the control levels. It can be concluded that IL-1 beta in itself is unable to induce proliferation in recently isolated cartilage cells. Our results suggest the possible existence of two different receptors for the different IL-1 beta activities. Hence, human articular chondrocytes respond differently to in vitro IL-1 beta exposure at different stages of differentiation.
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PMID:Influence of human recombinant interleukin-1 beta on human articular cartilage. Mitotic activity and proteoglycan metabolism. 195 99

Previous in vitro findings suggest the involvement of interleukin 1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus. The aims of the present study were to investigate the effects of single or repeated ip injections of recombinant IL-1 beta on blood glucose and glucose tolerance in vivo. Normal Wistar Kyoto rats were injected ip with a single injection of 4 micrograms/kg of the mature form of recombinant IL-1 beta (amino acids 117-269) or once daily on 5 consecutive days. Control rats were given vehicle and were fed ad libitum or pair-fed together with the rIL-1 beta treated rats. An ip glucose tolerance test (0.2 g D-glucose/100 g) was performed 2 h after injection of rIL-1 beta. A single injection of rIL-1 beta caused a mild depression in blood glucose and an improved glucose tolerance. Multiple injections of rIL-1 beta induced a diminished weight gain, a 24-28% reduction in food intake, a lasting mild depression of blood glucose (7 days) and a transiently impaired glucose tolerance on day 5. We conclude that systemic IL-1 should be considered an important regulator of glucose homeostasis in vivo.
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PMID:Repeated intraperitoneal injections of interleukin 1 beta induce glucose intolerance in normal rats. 203 44

After trauma, inflammatory, immunological and hormonal changes are well documented. Surgical intervention is a form of programmed trauma. Through the study of surgical patients, changes in early endogenous mediators of inflammation, immune response and tissue repair can be investigated. Here we analysed changes in serum levels of IL-1 inhibitors, IL-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha) and cortisol in patients undergoing elective surgery. C-reactive protein (CRP) was measured as a marker of the acute-phase response. Rises in serum levels of IL-1 inhibitors, IL-6 and cortisol were detected as early as 1 h after the intervention. Peak levels were reached between 2 and 5 h. Serum levels of IL-6 and cortisol remained elevated for several days implying a persistent production. Serum levels of IL-1 and TNF did not change after the intervention. CRP levels peaked on day 2. The communication system sustained by endogenous mediators is activated after surgery as shown by selective changes in IL-1 inhibitors, IL-6 and cortisol. These mediators have different kinetics in serum and IL-6 is not the only early mediator detected. Some IL-1 inhibitors might be involved in the immunological depression observed after major surgery, in the regulation of the inflammatory response or in tissue repair. IL-6 and cortisol seem to act synergistically to activate the acute-phase response. A systemic role for IL-1 and TNF is not evident, even if the possibility that these lymphokines may act locally is not ruled out.
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PMID:Selective and early increase of IL-1 inhibitors, IL-6 and cortisol after elective surgery. 207 May 56

Chronic Graft-versus-Host disease (GVHD) is characterized by overt immunosuppression. In addition, the skin is a major anatomical site affected in chronic GVHD for reasons not yet known. Increased collagen deposition, a mononuclear cell infiltrate in the dermis as well as loss of fat and appendages, are observed in the skin. The inflammatory cytokine IL-1 was shown to affect fibroblast proliferation and secretory activities. In the present study, IL-1 generation by dermal fibroblasts, of chronic GVHD or control mice, was assessed. It was shown that two sequential signals are needed for IL-1 generation by dermal fibroblasts; priming by lymphokines/cytokines followed by a challenge with LPS. A variety of recombinant lymphokines and cytokines (G/M-CSF, IL-2, TNF, IL-1 beta and IFNs alpha, beta and gamma) were shown to be efficient in priming dermal fibroblasts for IL-1 generation. IL-1 activity in dermal fibroblasts, most probably of the IL-1 alpha species, was located in frozen-thawed cell lysates or associated to the cell membrane, though not secreted into the culture fluids. Dermal fibroblasts from chronic GVHD mice manifested a pronounced depression in IL-1 generation upon stimulation with exogenous lymphokines/cytokines and LPS. This was observed over a wide range of concentrations of lymphokines/cytokines and LPS. The depressed ability of chronic GVHD fibroblasts to generate IL-1 was pronounced even after few passages of the cells in vitro, and upon stimulation in culture outside the suppressive milieu of the animal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Depressed IL-1 production by chronic GVHD dermal fibroblasts. 210 13

We have investigated the effects of interleukin 1 (IL-1) administration on the ability of neutropenic mice to resist Pseudomonas aeruginosa challenge in vivo. Cyclophosphamide-treated mice received human rIL-1 beta at 7.0, 0.7, or 00.7 micrograms/kg, according to different regimens, to be challenged with a lethal ip inoculum of pseudomonas cells 5 days after myelosuppression. The repeated exposure of the neutropenic mice to an overall cytokine dosage of 7.0 or 0.7 micrograms/kg during the 4 days after myelosuppression was found to optimally restore the animals' antibacterial resistance. However, when administered as a single injection 24 hr before challenge, the same dosages of IL-1 had lower or no effect in enhancing survival, primarily leading only to a reduction in the amount of antipseudomonal chemotherapy required for cure. The regimen of IL-1 administration conferring optimal protection also resulted in a decrease in the number of pseudomonas cells recovered from the peritoneal cavity of infected mice. This regimen accelerated hematopoietic recovery in cyclophosphamide-treated mice. Assay of serum colony-stimulating activity (CSA) revealed that (a) cyclophosphamide treatment alone significantly increased the level of circulating CSA, (b) administration of a single dose of IL-1 to neutropenic mice induced an early, further increase in serum CSA, followed by depression, (c) a biphasic pattern of CSA response was also evident in mice repeatedly treated with IL-1. These results suggest that regulation of hematopoiesis may have an important role in the induction of antibacterial resistance in myelosuppressed hosts repeatedly treated with low dosages of IL-1.
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PMID:Antibacterial resistance induced by recombinant interleukin 1 in myelosuppressed mice: effect of treatment schedule and correlation with colony-stimulating activity in the bloodstream. 211 38


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