Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021345 (infectious mononucleosis)
 3,358 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 20-month-old male with fulminant infectious mononucleosis and the X-linked lymphoproliferative syndrome (XLP) was studied. Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA) and EBV DNA were detected in various tissues. Despite a combined treatment with acyclovir, immunoglobulin, and methylprednisolone, the patient deteriorated rapidly. Following treatment with recombinant interferon-gamma (IFN-gamma), defervescence occurred and circulating EBNA-positive cells markedly decreased. IFN-gamma prior to treatment ranged from 10.8 to 24.5 U/ml in the patient's serum and increased linearly post exogenous IFN-gamma treatment. His natural killer (NK)-cell activity remained in the normal range throughout his illness but autologous EBV-infected cells were not killed in vitro by his peripheral blood lymphocytes (PBL). These results suggest that patients with the fatal infectious mononucleosis phenotype of XLP may produce endogenous IFN-gamma. Defective cytotoxic T cells against EBV-infected cells seem to be responsible for the fulminant infectious mononucleosis in this patient.
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PMID:Interferon-gamma in a family with X-linked lymphoproliferative syndrome with acute Epstein-Barr virus infection. 253 85

Accumulating data indicate that cytokines, peptides involved in regulation of both physiological and pathological immune responses, are produced predominantly at the site of local antigen stimulation. Cytokine-producing cells were detected at the protein level in human tonsil tissue obtained from children with recurrent tonsillitis or infectious mononucleosis (IM). Concomitant production of 19 different human cytokines, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (ra), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma) and transforming growth factor-beta 1-3 (TGF-beta 1-3), was identified at a single-cell level by indirect immunohistochemical staining procedures and use of carefully selected cytokine-specific antibodies (Ab). Fresh frozen sections were fixed with 4% paraformaldehyde and permeabilized by 0.1% saponin treatment, eluting cholesterol from the cell-surface membrane and the Golgi complex. The intracellular localization of all cytokines, except IL-1 and IL-1ra, was demonstrated by a characteristic local cytoplasmic perinuclear configuration in producer cells. In addition, the immunoreactivity for certain cytokines (IL-2, IL-4, IL-5, G-CSF and GM-CSF) was expressed on the cell membranes and extended over a large extracellular area encompassing the producer cell. Localization of the cytokine to the Golgi organelle was established by co-staining with a monoclonal antibody (mAb) specific to the Golgi complex. Both the extra- and intracellular cytokine staining reactions could be blocked by preincubation of the cytokine-specific Ab with the corresponding purified natural or recombinant cytokine. A complex cytokine pattern was established in both groups studied, where most T-helper type 1 (Th1) and Th2 lymphokines were expressed in the tonsils but at different frequencies and localizations. Cells expressing IL-4, IL-5, IL-10 and IL-13, (Th2 response) were evident at higher frequencies in recurrent tonsillitis compared to sections from IM, which were associated with a more pronounced IL-2, IFN-gamma and TNF-beta expression.
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PMID:Concomitant in vivo production of 19 different cytokines in human tonsils. 782 61

AIDS typically consists of three phases: (1) an acute, infectious mononucleosis-like syndrome followed by (2) a prolonged asymptomatic stage ending in (3) the appearance of frank AIDS. The asymptomatic phase may last for years and its presence suggests a persistent conflagration between the virus and the host's immune response. There is considerable evidence that an immune response develops but the response is ultimately inadequate. From the work of others as well as our own, we have constructed a hypothesis which attempts to explain some aspects of the immune response. We propose that HIV-1 preferentially infects a subset of CD4+ lymphocytes which are then either destroyed or altered in their biological functions. Further, we suggest that this subset represents the CD4+ TH1 lymphocyte population. By decreasing the quantity of IL-2 and interferon-gamma produced by TH1 lymphocytes, the production of cytokines by TH2 cells is increased. One of the cytokines produced by TH2 lymphocytes is IL-10, a polypeptide with significant inhibitory properties towards lymphocytes. Sera from patients with frank AIDS have significant lymphocyte inhibitory activities some of which operate through IL-10. Thus, a gradual shift to a TH2-type response and release of increasing amounts of inhibitors eventually prevents the host from replacing destroyed cells or mounting new and appropriate immune responses.
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PMID:Breaking the asymptomatic phase of HIV-1 infection. 791 Jun 37

To characterize the abnormalities of natural killer (NK) cells in childhood lymphohistiocytic syndrome (LHS), we investigated the number and cytolytic functions of circulating NK cells in 10 LHS children using flow cytometry, 51Cr-release and single-cell assays. In the active phase, the numbers of CD16+ or CD56+ cells and NK activity were normal in more than half of the patients or otherwise decreased. Despite the treatment with interferon-gamma (IFN-gamma) there was no significant increase in NK activity in the children with LHS: the values (mean +/- S.D.) of 32.2% +/- 14.2% became 35.0% +/- 13.3% (P > 0.05) when the control values changed from 45.5% +/- 8.5% to 54.2% +/- 10.1% after the stimulation. However, the NK cells normally responded to interleukin 2 (IL-2). In contrast, NK cells from 9 patients with infectious mononucleosis (IM) responded well to both IFN-gamma and IL-1 (P < 0.01). At the single-cell level, their NK cells had defective recycling capacity with normal killing capacity. The maximal recycling capacity (MRC) values (mean +/- S.D.) were 3.6 +/- 0.8 as compared to the control value of 5.5 +/- 0.9 (P < 0.01). Two of the patients studied had extremely high levels of serum IFN-gamma (9.8 U/ml and 158.0 U/ml) as compared to the control value of < 0.4 U/ml. NK cells may have been strongly stimulated by IFN-gamma in vivo, which probably yields superficially normal NK cell activity in the face of the absence of responsiveness to IFN-gamma but not to IL-2. The defective recycling may be another abnormality of NK cells in LHS.
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PMID:Absence of responsiveness to interferon-gamma but not to interleukin 2 and depressed recycling as natural killer cell abnormalities in childhood lymphohistiocytic syndrome. 808 21

Cytokine profile and production was studied at a single-cell level in cells obtained from 14 patients with acute infectious mononucleosis (IM), with less than 7 days of symptomatic disease, by use of cytokine-specific MoAbs and indirect immunofluorescence technique. In producer cells, all the studied cytokines, except IL-1, accumulated in the Golgi system, which resulted in a characteristic morphology of the staining. Less than one in a thousand mononuclear cells obtained directly from IM blood and stained within 2 h of sampling produced IL-2, interferon-gamma (IFN-gamma), IL-4, IL-5, IL-6, IL-10, GM-CSF, tumour necrosis factor-alpha (TNF-alpha) or TNF-beta, spontaneously. However, these cells were induced to cytokine synthesis by T cell receptor ligation in vitro using immobilized anti-CD3 MoAbs for 2-3 h restimulation under conditions which did not activate normal cells. By this approach 168 +/- 120 cells/10,000 peripheral blood mononuclear cells produced IFN-gamma as compared with 10 +/- 8 cells/10,000 non-stimulated cultured cells obtained from IM patients (P < 0.001) and 1/10,000 cells obtained from healthy controls, respectively. No induced production of IL-2, IL-3, IL-4, IL-5, IL-10, GM-CSF or TNF-beta was detected in IM cells obtained from peripheral blood by this restimulation. In contrast, a spontaneous cytokine production was evident in tonsil material obtained from four IM patients tonsilectomized because of respiratory obstruction. From this site 160 +/- 40 cells/10,000 cells produced IL-2, 40 +/- 30 cells IL-6, 30 +/- 30 cells TNF-beta and 35 +/- 25 cells IFN-gamma, respectively. No such spontaneous IL-2, IL-6, TNF-beta or IFN-gamma production was evident in control cells obtained from patients tonsilectomized because of chronic tonsil hyperplasia.
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PMID:Characterization of cytokine production in infectious mononucleosis studied at a single-cell level in tonsil and peripheral blood. 846 66

T cell immunodeficiency plays an important role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD) by permitting the unbridled expansion of Epstein-Barr virus (EBV)-infected B lymphocytes. However, factors other than T cell function may contribute to PTLD pathogenesis because PTLD infrequently develops even in the context of severe T cell immunodeficiency, and athymic mice that are T-cell-immunodeficient can reject EBV-immortalized cells. Here we report that PTLD tissues express significantly lower levels of IL-18, interferon-gamma (IFN-gamma), Mig, and RANTES compared to lymphoid tissues diagnosed with acute EBV-induced infectious mononucleosis, as assessed by semiquantitative RT-PCR analysis. Other cytokines and chemokines are expressed at similar levels. Immunohistochemistry confirmed that PTLD tissues contain less IL-18 and Mig protein than tissues with infectious mononucleosis. IL-18, primarily a monocyte product, promotes the secretion of IFN-gamma, which stimulates Mig and RANTES expression. Both IL-18 and Mig display antitumor activity in mice involving inhibition of angiogenesis. These results document greater expression of IL-18, IFN-gamma, Mig, and RANTES in lymphoid tissues with acute EBV-induced infectious mononucleosis compared to tissues with PTLD and raise the possibility that these mediators participate in critical host responses to EBV infection.
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PMID:Interleukin-18, interferon-gamma, IP-10, and Mig expression in Epstein-Barr virus-induced infectious mononucleosis and posttransplant lymphoproliferative disease. 1039 57

To identify the role of T cells in chronic active Epstein-Barr virus (EBV) infection, EBV and cytokine gene expression was quantified by use of real-time polymerase chain reaction (PCR) among 6 patients who fulfilled the diagnostic criteria for chronic active EBV infection. Four of these patients showed clonal expansion of EBV-infected T cells. Quantitative PCR for EBV DNA in peripheral blood of patients with symptomatic chronic active EBV infection showed higher copy numbers of virus (mean, 1.45 x 10(5) copies/mL) than were seen in blood from patients with infectious mononucleosis (3.08 x 10(3) copies/mL) or with EBV-associated hemophagocytosis (2.95 x 10(4) copies/mL). Fractionated CD3(+) HLA-DR(+) cells from patients with chronic active EBV infection contained higher copy numbers than did CD3(+) HLA-DR(-) cells. Quantitative PCR for cytokines revealed that interferon-gamma, interleukin (IL)-2, IL-10, and transforming growth factor-beta genes were expressed at higher levels in HLA-DR(+) than in HLA-DR(-) T cells. These results suggest that activated T cells in chronic active EBV infection expressed high levels of EBV DNA and both Th1 and Th2 cytokines. EBV-infected T cells may contribute to the unbalanced cytokine profiles of chronic mononucleosis.
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PMID:Epstein-Barr virus (EBV) load and cytokine gene expression in activated T cells of chronic active EBV infection. 1110 35

Serum levels of interleukin-16 (IL-16) were measured to investigate its role in the pathophysiology of hemophagocytic lymphohistiocytosis (HLH). Serum IL-16 levels in patients with acute HLH were significantly higher than those in healthy controls and patients with infectious mononucleosis. They returned to normal levels in the convalescent phase of the disease. In contrast to serum interferon-gamma (IFN-gamma) levels, serum IL-16 levels showed a gradual decrease over the course of the disease. Serum IL-16 levels showed a significant positive correlation with serum levels of soluble IL-2 receptor, IFN-gamma, and interleukin-18, body temperature, and serum lactic dehydrogenase (LDH) levels. An increase in IL-16 mRNA expression was detected in the liver of an HLH patient. These results suggest that IL-16 plays an important role in the pathophysiology of HLH by TH1 cell recruitment and activation at organs with inflammation.
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PMID:Increased IL-16 levels in hemophagocytic lymphohistiocytosis. 1534 83

Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis (IM). In addition, latent infections with EBV are associated with nasopharyngeal carcinoma (NPC) and Burkitt's Lymphoma (BL). Antibodies to several EBV-encoded early antigens (EA) are often observed in patients with NPC and BL, however, the role of EBV-encoded proteins in the etiology of these and other EBV-associated diseases is not completely understood. The EA complex encodes for at least six different viral enzymes including deoxyuridine triphosphate nucleotidohydrolase (dUTPase). dUTPase has recently been shown to modulate activation of human peripheral blood mononuclear cells in vitro (unpublished data). Therefore, these studies were designed to test whether dUTPase would modulate immune function in an in vivo model. Mice were injected with purified EBV dUTPase, and baseline immune function and sickness behaviors were measured. EBV dUTPase treatment inhibited replication of mitogen-stimulated lymphocytes obtained from treated mice. These lymphocytes were also less able to synthesize interferon-gamma after re-stimulation. In addition, treatment with dUTPase induced sickness behaviors. For example, as compared to control animals, dUTPase-treated animals lost body mass, had elevated body temperature, and displayed diminished locomotor activity. These data suggest that individual viral proteins may play a role in the pathophysiology of EBV associated disease.
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PMID:Epstein-Barr virus-encoded dUTPase modulates immune function and induces sickness behavior in mice. 1536 18

Most adults are asymptomatically infected with Epstein-Barr virus (EBV). Primary EBV infection is commonly associated with acute infectious mononucleosis (IM). T cell immune activation plays an important role in EBV-associated diseases. IM shows a mainly Th1-type profile, so Th1-type cytokines such as interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and lymphotoxin (LT) are moderately enhanced. We measured IL-2 and IFN-gamma in serum during acute phase of the disease and during convalescence. Sera were collected from 23 IM patients, 13 patients with similar clinical manifestations but without IM, and 10 healthy donors. The levels of IL-2, IFN-gamma and IL-12 were significantly higher in patients with acute IM than in healthy individuals. IL-2, IFN-gamma and IL-12 decreased during convalescence. These three cytokines may be useful as sensitive markers of IM during severe illness and its later phases.
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PMID:High Th1-type cytokine serum levels in patients with infectious mononucleosis. 1574 50


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