Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article briefly summarizes the literature regarding possible defects in cell-mediated immunity in the setting of chronic renal failure. It is difficult to precisely determine the proximate cause or level of such defects from most studies. Confounding variables include reports on mixed patient populations (predialytic chronic renal failure, hemodialysis patients, and peritoneal dialysis patients) and studies before and after the introduction of erythropoietin for end-stage renal disease patients. While it seems clear that lymphopenia, suboptimal responses to mitogens, abnormal cytokine gene expression, and abnormal IL-2R expression are seen in a number of dialysis patients, the role of uremia versus dialysis in producing these abnormalities is unclear. In addition, it is difficult to determine whether T cell abnormalities are primary or secondary to impaired function of other interacting immune cells, such as macrophages. Clinical implications of defects in cell-mediated immunity are additionally discussed.
 ...
PMID:T cell function in chronic renal failure and dialysis. 798 74

The sequence of activation of the components of the cytokine network subsequent to in vivo application of different dosages of IL-2 is still poorly understood. Although side effects of IL-2 therapy are dose dependent, the dose-response relationship for induction of potentially beneficial or harmful cytokine genes still remains to be studied. We examined the patterns of cytokine gene expression after treatment of chronic hepatitis B patients with various doses of IL-2 in a phase 1 trial. Total RNAs were isolated from PBMC harvested at various time points after s.c. injection of natural IL-2 ranging from 30,000 to 1,000,000 U. Dose-dependent effects on mRNA expression of IL-2, GM-CSF, IFN-gamma, TNF-alpha, and IL-6 were assessed using Northern blotting and slot blotting techniques. A single application of 30,000 U nIL-2 induced selective and long-lasting expression of IL-2, IFN-gamma, and GM-CSF genes, which was not accompanied by accumulation of TNF-alpha and IL-6 mRNAs. Larger dosages of IL-2 induced activation of monokine genes and were associated with systemic side effects. mRNA levels of the different cytokines related to biologic activity and correlated with expression of specific proteins and cellular parameters: IL-2 mRNA with soluble IL-2R serum levels and induction of lymphopenia, GM-CSF mRNA with induction of neutrophilia, and IL-6 mRNA with c-reactive protein serum concentrations. Taken together these data indicate unexpected immunoregulatory activities of very low and nontoxic dosages of IL-2 in vivo.
 ...
PMID:Biologic activity of low dosage IL-2 treatment in vivo. Molecular assessment of cytokine network interaction. 804 24

Lack of objective parameters to predict the clinical course and outcome are a major problem in managing the patients selected for BVAD-support as a bridge to heart transplantation. This study was intended to assess whether cellular immune parameters have a predictive value for the clinical result of VAD-support. Various cellular immune markers were monitored by multiparameter cytofluorometry in 30 patients who received a VAD system (Berlin Heart). We did not find significant differences in preoperative values of immune parameters between groups of survivors (n = 14) and non-survivors (n = 16). All 9 patients who died of septic multiple organ failure (MOF) had shown increased levels of T-cell activation (CD 71, CD 25, HLA-DR) as well as leukocytosis and 7 patients who died of noninfectious complications (mostly hemorrhage or cerebral complications) had exhibited T-lymphopenia. Seven of 9 patients who died of septic MOF had extremely decreased levels of HLA-DR+ monocytes (< 30%) while all 14 survivors and all 7 patients who died of noninfectious complications showed almost normal monocytic HLA-DR antigen expression, antigen-presenting capacity and cytokine secretion. These observations point to the reduced antimicrobial immunity ("immunoparalysis") in the non-survivors and may explain the fatal course of infection in these individuals. The in vitro results of restitution experiments call for new therapeutic strategies to improve the survival of VAD-patients.
 ...
PMID:Monitoring of the cellular immune system in patients with biventricular assist devices awaiting cardiac transplantation. 813 71

The dermatologist from Munich developed three differently called therapies; however, they basically show the same theory. They are the treatment with transoptin, tumor identification training for autologous immunocompetent cells (TI-TAI), and the autologous target cytokine (ATC) therapy. The ATC therapy is supposed to have a positive effect on all cancers and immunodeficiencies. Side effects are denied, although oncologists have noticed fatigue, fever, pain, lymphopenia, leukocytosis and others. The dermatologist supposedly establishes tumor cell and leukocyte cultures from blood and mixes them later on. The cytokines (ATC), produced by the lymphocytes, are harvested in 40 ampules and then subcutaneously injected. One cycle with the ATC therapy costs around 3000 DM. The dermatologist believes that tumor cells can only be immunologically identified during the dividing phase. He stimulates the cultured tumor cells to divide. At the same time he adds the autologous immunocompetent cells which should be trained to identify tumor cells and to produce cytokines. The dermatologist uses many terms unconventionally and imprecisely. The in-vitro training of lymphocytes for tumor defense with the method of the dermatologist is experimentally unproven. The production of the ATC preparations is kept secret. Also unclear are the mechanisms of action and the clinical efficacy. Besides neologisms, the dermatologist does not offer any scientific or clinical facts for his therapy of cancers.
 ...
PMID:[Autologous tumor therapy]. 821 Aug 72

More immunosuppressive drugs than ever have recently graduated from the laboratory to extensive clinical trials of their safety and efficacy in transplant patients. None of these drugs is perfect, but they control different forms of rejection in stringent animal models more effectively than other immunosuppressants, and these novel molecules suppress the immune system far more specifically than steroids and regimens that cause lymphopenia. Cyclosporin A and FK506 are the only drugs that selectively inhibit T-cell proliferation by blocking cytokine synthesis. The primary action of rapamycin appears to be inhibition of the actions of cytokines and growth factors on T, B, and some nonimmune cells. T and B cells are more sensitive than nonimmune cells to the depletion of purines and pyrimidines caused by mizoribine, mycophenolate mofetil, brequinar sodium, and leflunomide. Nucleotide depletion causes interruption of DNA synthesis and glycosylation of adhesion molecules in immune cells. Further differentiation of T and B cells after proliferation into fully functional immune cells is inhibited by unknown mechanisms of brequinar and deoxyspergualin. On the basis of preclinical studies, these drugs may effectively suppress clinical rejection that is acute (all), chronic (rapamycin, leflunomide, mycophenolate mofetil), or antibody mediated (brequinar, deoxyspergualin, mycophenolate mofetil, rapamycin, leflunomide). Some drugs (FK506, deoxyspergualin, mycophenolate mofetil, rapamycin, leflunomide) may reverse acute rejection refractory to conventional immunosuppression. Not only do these new drugs block different biochemical steps that normally lead to fully functional T and B cells after stimulation by alloantigen, but their toxicity profiles also differ. Results from preclinical studies predict that use of selected combinations of these drugs will be more effective, less nephrotoxic, less myelotoxic, and less broadly immunosuppressive than current regimens based on cyclosporine, T-cell depletion, steroids, and azathioprine.
 ...
PMID:Mechanisms of action of new immunosuppressive drugs. 858 21

Diabetes prone biobreeding rats display several abnormalities in T cell numbers, T cell function and T cell surface phenotype which are associated with the onset of spontaneous disease. One of the most pronounced abnormalities in these animals is a marked T cell lymphopenia which is evident in both CD4+ and CD8+ peripheral T cell subsets. To gain a better understanding as to the nature of T cell responses in these animals, we have utilized RT-PCR to analyze the cytokine mRNA profiles of mitogen activated peripheral T cells derived from lymphopenic and non-lymphopenic animals. Our results suggest that inheritance of the lymphopenia gene, Lyp, is associated with a unique cytokine profile most similar to that previously described for mouse medullary thymocytes. In addition, cell surface staining of peripheral T cells from diabetes prone animals revealed a high frequency of Thyl+ cells, which is characteristic of both thymocytes and recent thymic emigrants. Following thymectomy, T cell responsiveness to a number of different stimuli is greatly reduced on a cell for cell basis as is the absolute number of surviving T cells. Taken collectively, our results suggest that the majority of the peripheral T cell pool in these diabetic prone rats consists of short lived, recent thymic emigrants which most likely also contain the effector cells required for initiation of diabetes.
 ...
PMID:T cells from BB-DP rats show a unique cytokine mRNA profile associated with the IDDM1 susceptibility gene, Lyp. 873 69

Eighteen advanced cancer patients received weekday subcutaneous injections of recombinant interleukin-6 (rIL-6) for 4 weeks at escalating doses. Patients were evaluated for hematologic and immune system effects. Hematologic monitoring included WBC, differential, Hgb and Hct, platelet counts, and assessment of marrow and peripheral blood progenitors. Immunologic monitoring included evaluation of acute-phase reactants (APRs), immunophenotyping, serum cytokine levels, cytokine-induced proteins, and cytokine messenger RNA (mRNA). The maximal tolerated dose (MTD) was 8.0 micrograms/kg/day, with neurocortical toxicity as the major limiting factor. All patients became anemic, and most had fever and chills. APRs were increased throughout treatment. WBCs increased transiently on day 2; granulocytes and monocytes increased again through day 26, whereas lymphocytes decreased to baseline or lower levels. Platelets responded by day 12 and increased through day 26 at the MTD with no effect on colony-forming unit-megakaryocyte (CFU-Mk). Peripheral WBC and RBC progenitors were not affected but decreased in the marrow. T-cell percentages declined with little effect on absolute numbers; T-cell activation was seen. CD45RO+ T cells decreased, but there was no significant effect on CD8+ CD28+ T cells. Neither B cells nor natural killer (NK) cells were affected. However, evidence of monocyte effects included upregulation of CD71, induction of the cytokine-induced proteins 2-5A synthetase and neopterin, and increases in tumor necrosis factor-alpha (TNF-alpha) mRNA. Serum cytokines were undetected, and mRNA for IL-1 beta, IL-2, and interferon-gamma (IFN-gamma) was not induced; however, mRNA for IL-4 and IL-10 did increase suggesting activation of Th2-like T cells. One mixed tumor response was seen. We conclude that IL-6 alone has systemic activity on the immune system, as well as the hematopoietic system, which at the MTD, primarily involves induction of APR, activation and expansion of monocytes, and activation of Th2-like T cells.
 ...
PMID:Hematologic and immunologic evaluation of recombinant human interleukin-6 in patients with advanced malignant disease: evidence for monocyte activation. 881 98

IL-2 administration in vivo has been shown to increase CD4+ T cell counts in HIV+ patients. We have previously reported that PBMC from HIV-infected patients undergo marked spontaneous apoptosis in vitro. In this study, we examined the effect of IL-2 added in vitro upon culture-induced apoptosis in PBMC from 80 HIV-infected patients by flow cytometry. IL-2 at concentrations of > or = 10 U/ml significantly reduced spontaneous apoptosis in CD3+ T lymphocytes in patients but not in healthy volunteers. Interestingly, we observed that Bcl-2 expression in patient lymphocytes decreased rapidly upon in vitro culture while that in cells of healthy volunteers was relatively unaffected. The most significant decrease in Bcl-2 expression was noted in the apoptotic cell population. The IL-2-mediated reduction in lymphocyte apoptosis was found to be associated with the blocking of this culture-induced down-modulation of Bcl-2 expression. IL-2 did not induce significant expansion of lymphocytes during the culture period nor did it affect Fas Ag expression in patient cells, which were already expressing Fas maximally. These findings strongly suggest that IL-2 mediates its apoptosis-blocking effects via suppressing down-modulation of Bcl-2. Our findings also provide an experimental basis for the ongoing therapies utilizing this cytokine for slowing HIV disease progression.
 ...
PMID:IL-2 rescues in vitro lymphocyte apoptosis in patients with HIV infection: correlation with its ability to block culture-induced down-modulation of Bcl-2. 889 56

Recently, the synthetic immunomodulator Linomide (quinoline-3-carboxamide, LS 2616) was reported to prevent IDDM and insulitis in NOD mice. The mechanism for this protective effect is not known. The cytokine interleukin 1 (IL-1) may be a pathogenetic factor in the initial destruction of the beta-cells leading to IDDM. This study was undertaken to investigate the influence of Linomide on IL-1beta induced diabetogenic and hormonal changes in the rat in vivo, and on IL-1beta mediated synthesis of NO and inhibition of insulin secretion in isolated islets of Langerhans ex vivo. Normal male Wistar Kyoto rats received 4.0 microg/kg of recombinant human IL-1beta (rhIL-1beta) i.p. daily for 5 days with or without Linomide (8-9 mg/kg/day) in the drinking water. Litters of neonatal Wistar rats were pretreated for 3 days with injections of 10 mg/kg of Linomide i.p., and pancreatic islets of Langerhans were isolated for ex vivo studies. Linomide alone caused significant hypercorticosteronemia, hypoglucagonemia, lymphopenia and neutrophilia. Linomide had no effect on IL-1beta induced hyperglycemia, hyperglucagonemia, lymphopenia, neutrocytosis, or hypercorticosteronemia on day three and hypocorticosteronemia on day five. Further, Linomide did not prevent rhIL-1beta mediated reduction in insulin secretion or increase in NO synthesis ex vivo. In conclusion, Linomide does not seem to exert its protective effect on IDDM development via inhibition of interleukin 1 action on islet insulin release or NO production, but the increase in plasma corticosterone may contribute to the understanding of the immunomodulatory effects of Linomide.
 ...
PMID:Linomide increases plasma corticosterone in normal rats, but does not prevent the inhibitory action of IL-1 on beta-cells in vivo or ex vivo. 891 32

Anti-CD3 monoclonal antibody (mAb) OKT3 is immunosuppressive, but causes severe adverse effects during the first administration ("first-dose reaction"). These adverse effects are presumably caused by cytokine release that results from T-cell activation. In vitro, T-cell activation by anti-CD3 mAb requires interaction with monocyte Fc receptors. The Fc receptor for murine IgG1, Fc gammaRIIa, is polymorphic. In some individuals, murine IgG1 anti-CD3 mAb causes T-cell proliferation and cytokine release in vitro (high responders [HR]), whereas in individuals with the low-responder (LR) phenotype it does not. We have now investigated the role of this Fc gammaRIIa polymorphism in the release of cytokines in vivo and the occurrence of adverse effects after the administration of WT31, a murine IgG1 anti-CD3/T cell receptor mAb. WT31 caused an increase of plasma tumor necrosis factor-alpha in all four HR patients and none of the five LR patients. In all HR patients except one, plasma gamma-interferon and interleukin 6 also increased, and a first-dose response was observed, whereas no cytokine release or adverse effects occurred in any of the LR patients. WT31 caused lymphopenia in all HR and none of the LR patients. FACS analysis demonstrated that in HR patients, after the initial disappearance of CD3+ cells from peripheral blood, modulation of CD3 occurred, whereas in LR patients a high degree of coating of the lymphocytes was observed. Surprisingly, WT31 also induced a marked granulocytopenia, as well as a decrease of thrombocytes, in three of the four HR patients (and in none of the LR patients). These data provide direct clinical evidence that Fc receptor interaction determines the release of cytokines and the occurrence of adverse effects after administration of anti-CD3/T cell receptor mAb. Furthermore, these data suggest that tumor necrosis factor-alpha by itself is not sufficient to induce the first-dose reaction.
 ...
PMID:Role of polymorphic Fc receptor Fc gammaRIIa in cytokine release and adverse effects of murine IgG1 anti-CD3/T cell receptor antibody (WT31). 900 Jun 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>