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

Tumour necrosis factor (TNF), a polypeptide produced by mononuclear phagocytes, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in acute infectious diseases. To study further the potential role of TNF in infectious diseases, recombinant Escherichia coli (E. coli) derived human (r.HuTNF-alpha) and bovine TNF (r.BoTNF-alpha) were intravenously (i.v.) administered in dwarf goats. Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and haematological values were studied and compared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 microgram/kg i.v.). Following a single injection of 4 micrograms/kg of r.BoTNF-alpha, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and neutropenia followed by neutrophilia. The i.v. administration of a single injection of 4 micrograms/kg r.HuTNF-alpha induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasma trace metal concentrations when compared with r.BoTNF-alpha-treated goats. The TNF-alpha-induced symptoms were essentially the same as those that occurred after LPS administration. However, the time of onset of these changes after the injection of TNF-alpha was significantly shorter than after LPS. Moreover, the r.BoTNF-alpha induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF-alpha nor LPS caused severe haemo-concentration. Furthermore, no cross-tolerance between r.BoTNF-alpha and LPS could be demonstrated. We conclude that both r.BoTNF-alpha and r.HuTNF-alpha induce many of the physiologic, haematologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r.BoTNF-alpha, r.HuTNF-alpha and LPS in dwarf goats may indicate that both recombinant tumour necrosis factors have some homology with caprine TNF-alpha.
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PMID:Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha. 148 32

Blood counts of CD4 cells remain the best prognostic factor in patients infected with human immunodeficiency virus (HIV). However, the small number of infected cells contrasts with the importance of lymphocyte depletion. Several mechanisms might explain this depletion including: antibody-dependent cytotoxicity. Twenty to 50% of the antibodies produced in vitro by B lymphocytes are directed against HIV antigens, especially the gp120 and gp41 viral envelope antigen. If this cytotoxicity effect occurs in vivo, it could reduce of lymphocytes carrying the viral genome and partially explain the major lymphopenia in HIV-infected patients. It is not yet known whether the long-term effect of these antibodies is immunoprotective or deleterious, but they may play a protective role at least in the initial stages of the disease. autoimmunity. Sequence homology between the HLA II molecules and the glycoproteins of the viral envelope has been clinically and biologically documented in many manifestations of HIV infection. It has been suggested that alloreactivity, similar to the graft-versus-host reaction could be involved. In addition, programmed cell-death of the CD4 lymphocytes appears to be overactivated in HIV-positive subjects, possibly because the gp120 viral antigen perturbs the CD4-dependent signal for cell death. deleterious effects of cytokines. Tumour necrosis factor, for example, is known to play a role in the regulation of viral replication; it may favour the destruction of contaminated cells but also the initiation of provirus replication and integration into the cell genome. supra-antigens and/or infectious factors. Supra-antigenes, which can link with HLA molecules, are capable of oligoclonal activation without being "processed" in the cell presenting the antigen. This activation might affect cell death. Certain germ toxins could also play a role as cofactors. Cohort studies of asymptomatic HIV patients are needed to improve our understanding of these mechanisms. A therapeutic approach tailored to the stage reached by HIV-infected subjects will then be possible.
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PMID:[Mechanisms of lymphopenia in HIV infection]. 790 32

The rapid expansion in the therapeutic modalities available for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitides (AAV), with clear limitations in existing strategies, prompted us to undertake a review of novel therapies reported in MEDLINE and EMBASE. Tumour necrosis factor (TNF)-alpha antagonism with infliximab is described favourably in retrospective series and open-label trials. However, evidence from the WGET (Wegener's Granulomatosis Etanercept Trial) does not support the clinical use of etanercept, and a significantly higher malignancy rate following TNFalpha inhibition questions the role of this approach. Uncontrolled evidence alone supports remission induction with rituximab-mediated B-lymphocyte depletion and may be less effective in predominantly granulomatous AAV. Remission following T-lymphocyte depletion can be achieved with alemtuzumab and antithymocyte globulin, but it is not yet clear what the clinical role will be for these agents in AAV. In addition, these agents are associated with prolonged lymphopenia and pulmonary complications, respectively. Stem cell transplantation to support immune reconstitution following the use of such agents has been trialled in AAV, but studies included very few patients. Purine and pyrimidine antimetabolites mycophenolate mofetil and leflunomide are likely to play an important role in the treatment of AAV, but results supporting remission maintenance and induction in the former are limited to uncontrolled trials, such that their use remains experimental at this time. Similarly, 15-deoxyspergualin may provide an alternative to cyclophosphamide but awaits randomized controlled trial evidence. The MEPEX (MEthylprednisolone versus Plasma EXchange) trial supports plasma exchange in renal disease but this may be limited by pulmonary complications. Randomized controlled evidence also exists for intravenous immunoglobulin, although improvement may not be sustained. Antimicrobial therapy may be of use in Wegener's granulomatosis patients with predominantly upper respiratory tract involvement. Safety concerns, notably of infection and malignancy, were common and need to be explored in subsequent trials. In addition, concomitant immunosuppressants and non-standardized definitions were major limitations, and future studies of these and newer agents must follow agreed standards of study design and reporting to facilitate clearer interpretation of the circumstances (e.g. disease stage, severity or organ involvement) under which these agents perform optimally. Consequently, use is still limited to centres experienced in such agents and mostly in the context of clinical trials.
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PMID:Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis. 1841 84

Histone deacetylase inhibitors (HDACi) can modulate innate antiviral responses and render tumors more susceptible to oncolytic viruses (OVs); however, their effects on adaptive immunity in this context are largely unknown. Our present study reveals an unexpected property of the HDACi MS-275 that enhances viral vector-induced lymphopenia leading to selective depletion of bystander lymphocytes and regulatory T cells while allowing expansion of antigen-specific secondary responses. Coadministration of vaccine plus drug during the boosting phase focuses the immune response on the tumor by suppressing the primary immune response against the vaccine vector and enhancing the secondary response against the tumor antigen. Furthermore, improvement of T cell functionality was evident suggesting that MS-275 can orchestrate a complex array of effects that synergize immunotherapy and viral oncolysis. Surprisingly, while MS-275 dramatically enhanced efficacy, it suppressed autoimmune pathology, profoundly improving the therapeutic index.
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PMID:HDAC inhibition suppresses primary immune responses, enhances secondary immune responses, and abrogates autoimmunity during tumor immunotherapy. 2329 47