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)

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

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

Despite the fact that nucleoside analogues, such as aciclovir and ganciclovir, and DNA-polymerase inhibitors, such as foscarnet, have a proven antiviral effect on oropharyngeal-Epstein-Barr virus (EBV) replication, they have been unable to show any effect on the severity or duration of infectious mononucleosis (IM), a condition for which there is currently no established treatment. Clinical symptoms may be due to an EBV-induced polyclonal humoral, as well as cellular, immunoreactivity with limited pathology caused by viral replication itself. However, despite an extensive immune response, 90% of tested IM patients (n = 36) had a spontaneous outgrowth of in vivo EBV-infected B-lymphocytes at onset of disease, indicating lack of specific EBV-restricted cellular cytotoxicity at this time. Establishment of an EBV-specific T-lymphocyte response occurred 90-180 days after onset of disease (human leukocyte antigen-restricted cytotoxicity against EBV-infected B-cells). Thus, development of a specific cytotoxic response was a gradual and slow process. Assessment of cytokine pattern, at the single cell level, was performed by immunocytochemical technique and by enzyme-linked immunosorbent assay. This revealed an increased production of interleukin (IL)-2, interferon (IFN)-gamma, IL-6 and tumour necrosis factor (TNF) beta in all IM patients. Those with disseminated disease were characterized by lack of IFN-gamma production. This loss was selective since in vitro stimulation with superantigen, such as streptococcal pyrogenic exotoxin A, induced a normal response. These patients lacked signs of EBV-specific T-cell cytotoxicity in vitro. Treatment with intravenous or subcutaneous IFN-gamma, 1.5 MU every second day, in combination with intravenous immunoglobulin G (0.5 g/kg three times per week) and oral aciclovir, 800 mg 5 times daily, has shown promising results in some patients. Cytokine production in tonsil tissue in 4 patients with fulminant IM and respiratory tract obstruction showed a concomitant expression of IL-2, IFN-gamma, IL-6, TNF beta, transforming growth factor (TGF) beta 1-3, granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, IL-4 IL-1alpha, IL-beta and TNF alpha. The number of IL-2, IFN-gamma, IL-6 and TNF beta producing cells was significantly higher compared to tonsil tissue obtained from children with tonsillar hypertrophy. Thus, IM is associated with extensive local cytokine production. It is suggested that this extensive cytokine production is closely involved in the pathology of IM and that patients with atypical IM have a dysregulation in the cytokine network. However, the mechanism by which EBV-infected B-lymphocytes triggers this cytokine cascade is still unknown. These findings show the need for evaluation of patients with immunodeficiency and EBV-induced lymphoproliferative disorders and perhaps the introduction of new immunoregulatory treatment strategies.
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PMID:Clinical and immunological considerations in Epstein-Barr virus-associated diseases. 886 Mar 57

Cytokine profiles of CD4+ and CD8+ T-cell subsets were evaluated in 8 patients with infectious mononucleosis (IM). Intracellular detection of cytokines using flow cytometry revealed an expansion of IFN-gamma-expressing CD4+ T cells, and particularly CD8+ T cells, while IL-2 expressing cells were less frequently encountered when compared to healthy controls. Single TNF-alpha-expressing CD4+ and CD8+ T cells were likewise reduced and shifted towards IFN-gamma/TNF-alpha co-production. The predominant pro-inflammatory type 1-biased immune response during IM was emphasized by low frequencies of IL-10 expression in both T cell subsets, although some patients displayed elevated serum levels. Six months later, a decreased, but still elevated IFN-gamma expression within the CD8+ T cell subset, and an increased percentage of IL-2-expressing CD4+ and CD8+ T cells, reaching values shown for controls, were noted. Type 2-associated cytokines such as IL-4 and IL-13, as well as IL-6 and TNF-alpha were not significantly different when compared to controls at study entry and at follow-up. The striking expansion of IFN-gamma-producing CD8+ T cells with rather low expression of IL-10, appears to be a key factor for clinically overt disease, but is nevertheless compatible with successful control of the viral infection.
Eur Cytokine Netw
PMID:T cell cytokine profile during primary Epstein-Barr virus infection (infectious mononucleosis). 1279 12

Viral loads and cytokine responses Epstein-Barr virus (EBV) were measured in an 18-year-old boy with severe glandular fever complicated by a mild anaemia, severe thrombocytopaenia and neutropaenia. Hepatosplenomegaly was detected by abdominal ultrasound in the presence of significant hepatitis. Cytokine testing demonstrated elevated cell-mediated Th1 (IFN-gamma, IL-12, sTNFR1, CXCL10, CXCL9 and CCL3) and humoral Th2 (IL-4) immune responses. Serum antibodies to EBV virus capsid antigen (VCA) IgM and IgG antibodies were detected, together with a raised EBV DNA level (up to about 70,000 DNA copies/mL) in the acute phase of the illness. This EBV DNA load decreased rapidly in response to treatment with a combination of foscarnet, intravenous immunoglobulin and prednisolone, and the boy's symptoms settled eventually after approximately 50 days of illness, following this combined antiviral and immune-modulating therapy. Detailed immunological, virological, haematological and biochemical laboratory parameters are presented to document this patient's severe EBV disease and eventual recovery.
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PMID:Cytokine responses in a severe case of glandular fever treated successfully with foscarnet combined with prednisolone and intravenous immunoglobulin. 1903 55

IL-27 is a heterodimeric cytokine composed of p28 and Epstein Barr virus induced gene 3 (Ebi3) protein subunits. In the present study, we questioned whether murine gammaherpesvirus 68 (HV-68) could induce expression of Ebi3, p28, and IL-27 in this mouse model of an EBV-like infection. Cultured macrophages and dendritic cells exposed to HV-68 upregulated p28 mRNA expression and increased secretion of the p28 and IL-27 (p28+Ebi3) proteins. B220(+) and CD11b(+) cells also upregulated p28 mRNA expression following in vivo infection with this virus. Surprisingly, no significant increases in p28 or IL-27 protein production were observed in vivo during the acute or mononucleosis phases of the disease. The possibility that HV-68-induced upregulation of p28 mRNA expression primed cells for IL-27 secretion was suggested by the ability of a TLR4 agonist to augment cytokine production. When cultured macrophages and dendritic cells were exposed to virus plus a suboptimal dose of LPS, increased levels of p28 protein expression were observed. More importantly, when latently infected mice were challenged with a sublethal dose of LPS, augmented p28 and IL-27 protein production occurred. Using a model of sepsis, mice latently infected with HV-68 had exaggerated p28 protein production when compared to mice that were singularly infected or subjected to cecal ligation and puncture. Taken together, these studies define expression of HV-68 induced IL-27, and suggest that mice latently infected with this gammaherpesvirus will have exaggerated responses when confronted with other stimuli capable of inducing this member of the IL-12 family of cytokines.
Cytokine 2010 Aug
PMID:Interleukin-27 expression following infection with the murine gammaherpesvirus 68. 2049 22