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)

Antihistamines are frequently employed in the treatment of allergic rhinitis and urticaria-angioedema syndrome. We analyzed the in vitro effects of cetirizine on the immune response. To this end the proliferation of peripheral mononuclear cells induced by mitogen and by -CD3, -CD2, or -CD28 monoclonal antibodies has been studied. Since the plasma peak of cetirizine following ingestion of 10 mg is about 1 microgram/mL, the drug was tested in the cultures at the concentration of 0.1, 1, or 10 micrograms/mL. No influence of cetirizine on T cell proliferation was detected. We also evaluated the effect of cetirizine on the expression of the following markers expressed by T cells upon activation: lymphocyte markers ICAM-1, HLA-DR, and CD25 surface expression, alpha-1-acid glycoprotein has been also studied. There was no effect of cetirizine on the investigated immunologic parameters; these data acquire clinical relevance when related to previous reports showing a depression of the immunologic response exerted by other compounds such as ketotifen and theophylline and when related to the recent data about the modulation of ICAM-1 expression on eosinophils by cetirizine. Cetirizine does not affect ICAM-1 expression of lymphocyte membrane.
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PMID:Cetirizine does not influence the immune response. 134 75

Sixteen human T-cell lines were studied for the expression of a cell-adhesion molecule ICAM-1 and its counter-receptor LFA-1. The cell lines included 3 human T-cell-leukemia-virus-type-I (HTLV-1)-negative cell lines derived from acute lymphoblastic leukemia (ALL) and 13 HTLV-1-positive cell lines, 7 of them established from cord- or peripheral-blood T cells by in vitro transformation with HTLV-1, 2 derived from HTLV-1 carriers, and 4 derived from patients with adult T-cell leukemia (ATL). In sharp contrast to a basal level of ICAM-1 in 3 HTLV-1-negative ALL cell lines, strong induction of ICAM-1 was seen in all HTLV-1-positive T-cell lines except for MT-1, one of the 4 ATL cell lines used in the present study. On the other hand, the expression of LFA-1 (CD11a and CD18) was more or less similar among the cell lines with and without HTLV-1. Interestingly, however, 3 out of 4 ATL cell lines (TL-Om1, H582, HUT102) revealed striking depression of LFA-1 expression. Several lines of evidence strongly argued against direct involvement of the viral transactivator p40tax or some autocrine cytokines in the induction of ICAM-1 in HTLV-1-positive T-cell lines. It was also found that ICAM-1 and LFA-1 were involved in syncytium formation induced in the co-culture of HTLV-1-positive and HTLV-1-negative human T-cell lines. Implications of constitutive expression of ICAM-1 for certain clinical manifestations of ATL and of depression of either ICAM-1 or LFA-1 during progression of ATL are discussed.
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PMID:Strong induction of ICAM-1 in human T cells transformed by human T-cell-leukemia virus type 1 and depression of ICAM-1 or LFA-1 in adult T-cell-leukemia-derived cell lines. 135 35

The triggering of the TCR/CD3 complex by anti-CD3 (OKT3) antibody leads to the formation of T cell clusters. In cultures of T lymphocytes from most normal individuals, the peak of cluster formation occurs at 24 h, but with cells from patients with common variable immunodeficiency (CVI) it was seen earlier at 4-9 h; in addition, the clusters were larger than normal, particularly at 9 h. Cluster formation by CVI and normal cells was dependent on temperature and divalent cations, but did not require Fc receptors. Since OKT3 clustering is known to be dependent on the LFA-1/ICAM-1 adhesion system, the effect of monoclonal antibodies directed against these molecules was tested. A potent inhibitor was the antibody against the common beta chain of the integrin family (CD18), but of four MoAbs against the alpha chains (CD11), three inhibited and one stimulated T cell aggregate formation. Increased expression of LFA-1 or ICAM-1 on CVI patients' T cells could not be demonstrated. The accelerated clustering was therefore probably due to an increase in the proportion of cells carrying the activated form of LFA-1. The formation of large numbers of homotypic lymphocyte clusters might reduce the effective interaction between B and T cells, thus contributing to the depression of immunoglobulin synthesis observed in this disease.
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PMID:LFA-1-dependent OKT3-driven T cell clusters in common variable immunodeficiency. 173 36

Cognitive disorders associated with HIV infection may be due to focal lesions (lymphoma, toxoplasmosis, progressive multifocal leukoencephalitis, etc.), metabolic encephalopathy (e.g. hepatic insufficiency) or psychiatric disorders (depression). In the absence of such causes a "cognitive and motor syndrome associated with HIV infection" has been defined on clinical criteria (Working group of the American Academy of Neurology, 1991). This syndrome is not consistently associated with any specific lesion. Neither the multifocal encephalitis of HIV or CMV infection nor the diffuse leukoencephalopathy associated with HIV are the only causes. The existence of a neocortical neuronal loss has been suggested by several retrospective studies, but our prospective study has not shown cortical or subcortical atrophy. Measurement of neuronal density in Brodmann's areas 4,9 and 40 has not revealed a significant loss either global, by layer, or by column. The only constant lesion was gliosis of the cortex and white matter. Neuronal loss, therefore, is not indispensable to the occurrence of cognitive disorders in AIDS. The mechanism of dementia might be: dysfunction of cortical neurons (dendritic abnormalities, virus/neurotransmitter competition); subcortical dysfunction, as suggested by the high density of microglial nodules in that region; white matter lesions which could be due to abnormalities in the blood-brain barrier. The expression of cell adhesion molecules (VCAM-1, VLA-4, ICAM-1 and LFA-1) by endothelial cerebral cells is not significantly different in AIDS patients, demented or not, and in patients with multiple sclerosis. In contrast, the expression of VCAM-1 by astrocytes is significantly increased in demented AIDS patients compared with non demented ones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[HIV and dementia: neuropathology]. 747 30

We investigated the effect of combined treatment with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies (MAbs) in the immune reaction to Moloney-murine-sarcoma-virus(M-MSV)-induced tumors, which spontaneously regress due to the generation of a strong virus-specific cytotoxic-T-lymphocyte(CTL) response. Repeated systemic administration of both MAbs to M-MSV-injected mice enhanced tumor growth and delayed regression, while treatment with a single MAb had a similar, though less pronounced, effect. The immune depression achieved could not be attributed to lymphocyte depletion, because no reduction in the total number of leukocytes was detected in the peripheral blood or spleen of these mice. However, anti-LFA-I MAb, alone or in combination with anti-ICAM-I MAb, prevented lymphocyte homing in tumor-draining lymph nodes. Cytofluorimetric analysis disclosed a profound down-modulation of LFA-I and ICAM-I molecule expression on T cells following in vivo MAb treatment. Moreover, in anti-LFA-I MAb-treated mice, the receptor was coated to saturation, while anti-ICAM-I MAb treatment brought about ICAM-I-molecule-coating levels below saturation. Evaluation of M-MSV-specific CTL precursor (p) frequency in lymphoid organs of mice receiving combined MAb treatment showed that CTL generation was greatly reduced 10 days after M-MSV injection, and returned to control levels by day 15. Our findings indicate that systemic administration of MAbs to LFA-I and ICAM-I molecules brings about a strong immune suppressive effect which is mainly due to a block in T-lymphocyte re-circulation, and activation by tumor cells. However, this immune-depressive effect is only temporary, and strictly dependent on continuous MAb administration. Thus, our data suggest that treatment with anti-LFA-I and anti-ICAM-I MAbs combined is unable to induce T-cell tolerance in a highly immunogenic system.
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PMID:Role of anti-LFA-1 and anti-ICAM-1 combined MAb treatment in the rejection of tumors induced by Moloney murine sarcoma virus (M-MSV). 772 48

Chromones are frequently employed in the treatment of allergic rhinoconjunctivitis and asthma. Following our recent investigations concerning the influence of some antiallergic drugs, such as cromoglycate sodium, steroids, oxatomide and ketotifen (H1 antihistamines), and theophylline, on the immune response, in the present study we analyzed the in vitro effects of a new chromone derivative, nedocromil, on the immune response. To this end, the proliferation of peripheral mononuclear cells (PMNCs) induced by mitogen (PHA) and by CD3, CD2 or CD28 monoclonal antibodies (MAbs) has been studied. Since the effects of nedocromil on immunological parameters are achieved at 10(-7) mol/l, in the experiments herein reported the drug was tested in the cultures at concentrations of 10(-8), 10(-7) and 10(-6) mol/l. Furthermore, the effect of nedocromil was evaluated on the surface expression of the following markers expressed by PMNCs upon activation: ICAM-1 (CD54), LFA-1 and alpha 1-acid glycoprotein (alpha 1-AGP). The results of the present investigation showed no effect of nedocromil on these immunological parameters. These data acquire clinical relevance when related to previous reports showing a depression of the immunological response exerted by other compounds, such as ketotifen, theophylline and steroids.
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PMID:Nedocromil sodium and the immune response. 791 48

Between January 1991 and January 1993, 265 patients who fulfilled the CDC criteria of the working case definition of Chronic Fatigue Syndrome (CFS) have been observed at our Institution and submitted for clinical and laboratory evaluation. One hundred and sixty-three patients were females and 102 males, the median age was 35 years (range 4-55 years); all patients reported profound and prolonged fatigue, lasting for a median of 3 years (range 6 months-10 years), preceded or accompanied at appearance by fever in 185 cases, and neuropsychologic problems including inability to concentrate, difficulty in thinking, confusion, irritability, forgetfulness, and depression. The fatigue was so severe that it required 102 patients to stop their working activities for a period of time ranging from 3 months to 2 years (range 7 months). In 40 consecutive patients a comprehensive immunologic testing by single and two-colour flow cytometry was performed and results compared with a group of 35 healthy, age- and sex-matched controls. Whilst no significant differences were found in the absolute numbers of circulating total T cells (CD3+) and of total helper/inducer (CD4+) or suppressor/cytotoxic (CD8+) T cells, an evident reduction in CD3-/CD16+ and CD57+/CD56+ NK lymphocytes along with an expansion of the CD8+/CD56+ and CD16-/CD56+ NK subsets, were found in the CFS group. In addition, CD56+ NK cells from CFS subjects were found to express an increased amount of cell adhesion molecules (CD11b, CD11c, CD54) and activation antigens (CD38). Both the percentage and absolute numbers of CD4+ T cells bearing the CD45RA antigen appeared significantly reduced in CFS patients, and CD4+ T lymphocytes from CFS subjects displayed an increased expression of the intercellular adhesion molecule-1 (ICAM-1/CD54). Finally, the total numbers of circulating (CD19+) B lymphocytes, were significantly higher in CFS cases than in controls, and in 11 out of 30 CFS patients the increase in circulating B cells was sustained by the expansion of the CD5+/CD19+ subset of B lymphocytes. We conclude that CFS is a syndrome not previously described in Italy, with already known clinical characteristics and appears to be associated with several immunologic abnormalities, including those reported previously in cohort of patients from different countries. We also show for the first time that CD56- NK cell subsets from CFS patients display an abnormally increased expression of cell adhesion molecules and activation markers.
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PMID:Immunological abnormalities in patients with chronic fatigue syndrome. 799 49

This study evaluated the efficacy and mode of action of rapamycin (RPM) in a model of accelerated (24-hr) rejection of LBNF1 cardiac allografts in specifically sensitized LEW rats. RPM treatment (0.25 mg/kg/day i.p.) between the day of sensitizing skin grafts (day -7) and subsequent heart (day 0) transplantation (Tx), abrogated fulminant rejection and prolonged cardiac allograft survival to 46 +/- 22 days (mean +/- SD, P < 0.0001). The delayed introduction of RPM until day -2 or day -1 was equally effective, whereas treatment initiated after cardiac Tx was ineffectual. Untreated accelerated rejection was associated with strong production of circulating IgM, whereas an IgG alloantibody response was not detected until after rejection was complete. RPM therapy (day -7 to -1) diminished this systemic IgM response and prevented the switch from IgM to IgG alloantibody production. Immunohistologic evaluation at 24 hr after cardiac Tx showed that compared with untreated hosts RPM treatment largely abolished intragraft cellularity, and was associated with decreased mononuclear and endothelial cell activation. Specifically, Ia and ICAM-1 upregulation was abolished, and no cells elaborating IL-2 or IFN-gamma were detected. In addition, RPM treatment prevented intragraft production of the proinflammatory cytokines IL-1 beta, IL-6, and IL-8. The effects of RPM therapy on recipient cellular responses were evaluated in vitro by mixed lymphocyte reaction. Surprisingly, the donor-specific proliferative response of cells from RPM-treated hosts at 1 or 7 days after Tx was markedly increased, compared with cells from rejecting, untreated controls, and bioassay of IL-2 within supernatants of MLR cultures showed comparable levels of IL-2 in both groups. The effects of RPM upon adhesion properties of lymph node lymphocytes were also tested in an in vitro binding assay. The binding of naive cells to sections of cardiac allografts collected from RPM-treated hosts at 24 hr post-Tx was decreased compared with that in untreated recipients. Interestingly, the binding of mononuclear cells to high endothelial venules of peripheral lymph nodes in RPM-treated hosts remained relatively high. Thus, treatment with RPM prevents and/or erases the sensitization, which otherwise leads to accelerated allograft rejection. Abrogation of allograft injury by RPM was associated with profound and long-lasting depression of host IgM and IgG alloantibody responses in the circulation, and selective downregulation of host cellular immunity and endothelial activation at the graft site. In contrast, antigen alloreactivity and endothelial adhesivity in peripheral lymphoid tissues were spared, indicating novel and potent selective effects of RPM therapy in allograft recipients.
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PMID:Abrogation by rapamycin of accelerated rejection in sensitized rats by inhibition of alloantibody responses and selective suppression of intragraft mononuclear and endothelial cell activation, cytokine production, and cell adhesion. 815 43

Cardiac dysfunction occurs after thermal injury but the pathogenesis is nuclear; leukocytes have been implicated in the pathogenesis of multiorgan dysfunction after burn injury. White blood cell activation and entry into tissue involve the use of a number of adhesion molecules, including intercellular adhesion molecule (ICAM)-1, CD54. We asked the question: will administration of the monoclonal antibody (R6.5) directed against ICAM-1 alter the cardiac dysfunction which we have previously shown to occur after thermal injury? Previously instrumented New Zealand White rabbits were anesthetized and given a full-thickness burn over 30% of the total body surface area by applying brass probes heated to 100 degrees C to the animals' backs for 15 sec. Animals were monitored for 24 hr and given lactated Ringer's (LR) solution (4 cc/kg/% burn, Parkland formula) with additional LR given to maintain cardiac output and urine output. Three experimental groups were studied: sham burn controls had catheters placed and were monitored for 24 hr (N = 8); burn rabbits were divided into vehicle treated (saline, 1 ml/kg, N = 6) or R6.5 treated (2 mg/kg, N = 6). Vehicle or antibody was administered 30 min postburn and every 8 hr until 24 hr postburn; at this time, rabbits were sacrificed and hearts were harvested for in vitro assessment of contractile performance (Langendorff). Compared to values measured in sham burn controls, burn injury caused cardiac contractile depression as indicated by a fall in left ventricular pressure (LVP) (77 +/- 2 vs 56 +/- 3 mm Hg, P = 0.01), +dP/dt (1223 +/- 64 vs 842 +/- 64 mm Hg/sec, P = 0.001), and -dP/dt (973 +/- 63 vs 666 +/- 42 mm Hg/sec, P = 0.01). Administration of R6.5 significantly improved cardiac contractile function compared to the vehicle-treated burns as indicated by higher LVP (67 +/- 2 mm Hg, P > 0.05), +dP/dt (1017 +/- 33 mm Hg/sec, P > 0.05), and -dP/dt (858 +/- 40 mm Hg/ sec, P > 0.05) than values measured in vehicle-treated burns. These results suggest that ICAM-1-mediated WBC activation and/or tissue entry are involved in the pathogenesis of cardiac dysfunction following thermal injury.
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PMID:Monoclonal antibody to intercellular adhesion molecule-1 reduces cardiac contractile dysfunction after burn injury in rabbits. 880 73

Leukocytic infiltrates are a morphologic feature of most solid tumors, including uterine cervical intraepithelial neoplasia (CIN) and invasive carcinoma. We have studied 50 cases of CIN I, CIN II, CIN III, invasive carcinoma and normal controls in order to evaluate the inflammatory response. Two markers--CD68, a macrophage-specific marker, and ICAM-1, present on leukocytes, blood vessels and epithelial cells--were employed. Results have demonstrated similar inflammatory cell counts in normal, CIN II and CIN III lesions by both markers, and lower counts for CIN I. Invasive carcinomas demonstrated a statistically significant increase in infiltrate density by both CD68 (p < 0.002) and ICAM-1 (p < 0.05). Macrophage density by either marker did not correlate with Human Papillomavirus (HPV) presence, specific type, or evidence of co-infection with several types. We conclude that the inflammatory response to cervical intraepithelial-neoplasia is inadequate. The elevated cell counts in invasive carcinomas may reflect a reaction towards invasion rather than tumor-specific immune response. Depression of inflammation in CIN I lesions may be associated with active viral replication in these lesions.
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PMID:Inflammatory response in cervical intraepithelial neoplasia and squamous cell carcinoma of the uterine cervix. 934 55


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