Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of the human immunodeficiency virus (HIV) to replicate in CD+ T lymphocytes and mononuclear phagocytes(MP) is strongly influenced by immunoregulatory cytokines. In the T cell system, interleukin-2 (IL-2) provides a mitogenic signal leading to both cell proliferation and virus replication. Among other HIV-inductive cytokines, only tumor necrosis factor-alpha or -beta (TNF-alpha/-beta) have been shown thus far to trigger virus expression both in T cells and MP. The mechanism of action of TNF involves the activation of the cellular transcription factor NF-kB which binds to specific consensus sequences present in the enhancer region of the HIV proviral LTR. In addition, several other cytokines (including colony stimulating factors, IL-1, IL-3, and IL-6) have demonstrated upregulatory effects on HIV production in MP, whereas nonimmune interferons (INF-alpha/-beta) have been shown to suppress HIV replication in T cells and MP by acting at different phases in the virus life cycle. Finally, cytokines such as TGF-beta, IFN-gamma, and IL-4 have demonstrated either upregulatory or suppressive effects on virus expression depending on the experimental conditions. This scenario indicates that HIV expression is under the control of a complex network of immunoregulatory cytokines, in addition to its own endogenous regulatory proteins, suggesting that new pharmacologic strategies may be aimed at either mimicking or interrupting cytokine-dependent virus expression. In this regard, a number of different physiologic and pharmacologic agents capable of interfering with cytokine-mediated events, including glucocorticoids, anti-oxidants, such as N-Acetyl-L-Cysteine (NAC), and retinoic acid (RA) have already been shown to profoundly affect HIV replication in vitro.
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PMID:The effect of cytokines and pharmacologic agents on chronic HIV infection. 154 Apr 7

Gamma interferon (gamma-INF) production was studied and two-color fluorescence flow cytometry analysis was done on the peripheral blood mononuclear cells (PBMC) in allogeneic bone marrow transplant recipients. Gamma INF was not detected in any patients within a year after transplantation whether PBMC was stimulated with PHA or not. A year after transplantation, gamma-INF was produced in the normal level in the stimulated and unstimulated PBMC. The number of suppressor-inducer T cells (CD4+2H4+) was decreased and that of suppressor T cells (CD11+CD8+) was normal. The numbers of helper-inducer T cells (CD4+4B4+) and helper T cells (CD4+2H4-) were normal. The numbers of activated helper-inducer T cells (CD4+HLA-DR+) and suppressor-cytotoxic T cells (CD8+HLA-DR+) were elevated. In the NK cells, Leu7+ CD16-cells were elevated, whereas Leu7+CD16+ cells and Leu7-CD16+ cells were normal. Leu7+CD8+ cells were elevated. These results indicated immunodeficiency after transplantation.
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PMID:Gamma interferon production and two-color fluorescence flow cytometry analysis of peripheral blood mononuclear cells in allogeneic bone marrow transplant recipients. 210 21

We have recently shown that, in unfractioned peripheral blood mononuclear cells (PBMCs), the cross-linking of CD4 molecules (CD4XL) is sufficient to induce T-cell apoptosis. However, the underlying mechanism for the CD4XL-mediated T-cell apoptosis is largely unknown. Several recent studies have shown that Fas antigen (Ag), a cell-surface molecule, mediates apoptosis-triggering signals. We show here that cross-linking of CD4 molecules, induced either by anti-CD4 monoclonal antibody (MoAb) Leu3a or by human immunodeficiency virus-1 (HIV-1) envelope protein gp160, upregulates Fas Ag expression as well as Fas mRNA in normal lymphocytes. Addition of the tyrosine protein kinase inhibitor genistein or of the immunosuppressive agent cyclosporin A abrogated these effects. The upregulation of Fas Ag closely correlated with apoptotic cell death, as determined by flow cytometry. In addition, CD4XL resulted in the induction of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the absence of interleukin-2 (IL-2) and IL-4 secretion in PBMCs. Both INF-gamma and TNF-alpha were found to contribute to Fas Ag upregulation and both anti-IFN-gamma and anti-TNF-alpha antibodies blocked CD4XL-induced Fas Ag upregulation and lymphocyte apoptosis. These findings strongly suggest that aberrant cytokine secretion induced by CD4XL and consequent upregulation of Fas Ag expression might play a critical role in triggering peripheral T-cell apoptosis and thereby contribute to HIV disease pathogenesis.
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PMID:Cross-linking of CD4 molecules upregulates Fas antigen expression in lymphocytes by inducing interferon-gamma and tumor necrosis factor-alpha secretion. 752 37

The neuropathology associated with HIV (Human Immunodeficiency Virus) infection is one of the major complications of this disease. The virological and cellular mechanisms by which HIV infection induces motor and cognitive disorders remain unknown. This lack of understanding of the pathophysiology is partly due to the difficulty of experimental analysis in man because only post-mortem samples from terminal phases of the disease and cerebrospinal fluid samples are available. Two animal models, very closely resembling human HIV infection, are available: the cat model infected by FIV (Feline Immunodeficiency Virus) and the macaque model infected by the SIVmac (Simian Immunodeficiency Virus) which have enabled us to conduct a longitudinal study of encephalopathy during primo-infection and the asymptomatic and pre-AIDS (Acquired Immune Deficiency Syndrome) phases. In the cat-FIV model, which presents the advantage of being non-infectious to man, and therefore easier to manipulate, it was shown that infected cats develop behavioural abnormalities and a neuropathology which resemble HIV dementia. Central nervous system lesions induced by FIV are similar to those of HIV infection apart from the absence of multinucleated giant cells. This model was used to analyse the relationship between CNS lesions and the viral load of the brain and showed that the severity of the lesions contrasted with a low viral load. The pathophysiology of SIVmac infection in the rhesus macaque is almost identical to human infection with a more rapid course, since the duration of the asymptomatic phase is 6 months to 5 years, depending on the animal. We studied the relationship between lesions, viral load and cytokine production (IL-1 beta, IL-2, IL-6, TNF alpha, INF gamma, TGF-beta 1) within the CNS. Our results show early, low-grade and constant infection of the brain. The dissociation between the viral load and the lesions observed is our favour of an indirect mechanism for the pathogenesis of these lesions. The relationship between lesions and the cytokine profile studied shows the importance of glial cells in the pathogenesis of the lesions.
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PMID:[Contribution of animal models in the understanding of AIDS encephalopathy]. 938 13

Lymphokine activated killer (LAK) cells are capable of killing not only malignant cells but also hyphal form of Candida albicans in vitro. When peripheral blood mononuclear cells (PBMC) from normal healthy donors were cultured for 72-96 hrs with 1,500 international unit (IU)/ml interleukin-2 (IL-2), marked LAK activity was induced. However, even prior to IL-2 activation, PBMC isolated from some normal subjects and those from almost all individuals who are infected by human immunodeficiency virus type 1 (HIV-1) exhibited significant levels of anti-fungal activity. Such pre-activation ("in situ") antifungal activity of PBMC decreased during the initial 48 hrs of IL-2 activation. PBMC from HIV-1 seropositive subjects showed higher levels of "in situ" anti-fungal activity than normal PBMC did. After a decline of "in situ" activity during the initial 48 hours, LAK activity gradually increased and reached near maximal levels by day 4 and remained more or less constant until day 6. No significant difference was observed between the LAK activity of normal and HIV-1(+) PBMCs on days 4-6. In IL-2 activated normal and HIV-1(+) PBMC cultures, both CD4 and CD8 T cells produced IL-2, INF-gamma as well as TNF-alpha. Production of IL-2 by both CD4 and CD8 T cells was suppressed in HIV-1(+) PBMC cultures, but no significant suppression of INF-gamma production was noted. Meanwhile, TNF-alpha production by CD4 was very much suppressed but no significant changes in TNF-alpha production by CD8 T cells was noted in HIV-1(+) PBMC cultures.
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PMID:Anti-fungal and cytokine producing activities of CD8 + T lymphocytes from HIV-1 infected individuals. 973 53

Idiopathic interstitial pneumonitis (IP), characterized by lymphocytic infiltration of the lung and pulmonary dysfunction, is a major noninfectious complication of human immunodeficiency virus (HIV) infection. The role of the CD4+ and CD8+ T cell populations and INF-gamma in the development of IP were analyzed using a murine model of retroviral-associated IP. Infected mice depleted of CD8+ T cells developed IP similarly to untreated infected mice, suggesting that the CD8+ T cell population does not play a role in IP. Furthermore, depletion of CD8+ T cells did not alter the level of viral RNA in lungs, suggesting that cytotoxic T cells may not serve a role in controlling virus burden in lungs. In contrast, depletion of CD4+ T cells in infected mice prevented the development of IP and inhibited inflammatory cytokine expression, suggesting that CD4+ T cells are important for the development of IP. IFN-gamma -/- mice infected with virus for 10 weeks developed IP, although the severity of lymphocytic infiltration was substantially reduced compared to infected wild-type mice. The data suggest that persistent viral antigen in the lung may drive a CD4+ T cell-mediated immune response, resulting in the chronic production of IFN-gamma which amplifies a chronic inflammatory response in the lung resulting in tissue injury.
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PMID:Role of T cell subsets in the development of AIDS-associated interstitial pneumonitis in mice. 1064 64

The hyperimmunoglobulin E syndrome was discribed for Buckley, and it also called the Job syndrome. There are two types: dominant autosomal and recessive autosomal. It is a primary, rare and complex immunodeficiency, characterized clinically by recurrent skin abscesses for Staphylococcus aureus, recurrent pneumonia, and pneumatoceles, hypereosinophylia, high serum levels of immunoglobulin E (> 2,000 Ul/mL), early eczema and late loss of primary dentition. Recently a STAT3 mutation has been described as origin of dominant autosomal hyperimmunoglobulin E syndrome. Since 1972, 250 cases have been reported around the world. The diagnosis is done with the Grimbacher criteria and the prognosis depends on the opportune diagnosis and treatment. The incidence is same in women and men. The differential diagnosis is with allergic bronchopulmonary aspergillosis, chronic granullomatose disease, T cell lymphoma, and atopic dermatitis. The treatment is with prophylactic antibiotic, intravenous immunoglobulin or recombinant INF gamma.
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PMID:[Hyper IgE syndrome. Opportune diagnosis and management]. 1869 52

Chronic hepatitis C (CHC) and end-stage liver disease are becoming an increasingly common cause of mortality in patients with congenital bleeding disorders, especially in the HIV-coinfected group. Combination of pegylated interferon (Peg-IFN) and ribavirin has recently become the treatment of choice for CHC. In this study, we evaluated the safety and efficacy of combination therapy with Peg-IFN plus ribavirin for the treatment of CHC in human immunodeficiency virus (HIV)- and HIV+ patients with congenital bleeding disorders. Between 2000 and 2004, 50 (18-68 years old) patients with CHC (19 HIV+) from two hemophilia centers were included in the study. They were treated with weekly subcutaneous administration of Peg-INF-alpha combined with 800-1,200 mg ribavirin daily, for 24-48 weeks depending on viral genotype. Response was evaluated at weeks 12, 24, 48 (end of treatment response) and 72 had sustained virological response). Overall, 22/50 patients (43.8%) had end of treatment response and 20/50 (40%) sustained virological response. HIV- patients responded similarly to the general population (58.1%), while HIV+ patients had very low response rates (10.5%). The high rate of discontinuation (36.9%) as a result of side effects contributed to the observed low response rate in the HIV+ group. The only factor strongly associated with sustained virological response in the HIV- patients was the reduction of HCV RNA at 12 weeks (p = 0.001). Patients with viral genotypes other than 1 had higher SVR rates, but this was not found to be statistically significant. Peg-INF plus ribavirin is safe for the treatment of CHC monoinfected patients with inherited bleeding disorders, with similar response rates to nonhemophiliacs. On the contrary, in HIV coinfected hemophilic patients under highly active antiretroviral therapy it is associated with severe toxicity and very poor sustained virological response rates. Careful evaluation and several considerations are needed before starting treatment in this population.
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PMID:Pegylated interferon plus ribavirin combination therapy for chronic hepatitis C in patients with congenital coagulation disorders. 1882 74

The protozoon parasite Cryptosporidium parvum is an important cause of diarrhea in farm animals, but it can also infect other animals and humans. In this case report, oocysts of Cryptosporidium spp. were microscopically detected by modified Ziehl-Neelsen staining in the feces of a 9 day old Arabian colt presented with yellowish, foul smelling, diarrhea and fever of 40 degrees C. PCR and sequencing of the isolate revealed C. parvum (bovine genotype). Hemato-chemical analysis of the foals blood revealed a marked hypogammaglobulinaemia (IgG 108mg/dl). The colt responded well to a supportive therapy and administration of plasma (until a gammaglobulin-concentration of 620 mg/dl was reached) and was released in good health from the clinic after 10 days. Follow-up testing for Cryptosporidium oocycsts remained negative. Cryptosporidiosis with life-threatening diarrhea is a rare diagnosis in foals in Switzerland. Immunodeficiency increases the risk for cryptosporidiosis. We hypothesize that the low concentration of gammaglobulins together with the weak INF-gamma response normally observed in young foals may have favored the clinical manifestation with diarrhea. Foals with diarrhea should be screened for cryptosporidia with specific tests.
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PMID:[Cryptosporidiose (C. parvum) in a foal with diarrhea]. 1916 Jan 67

The objective of this study was to evaluate the efficacy and safety of pegylated interferon (PEG-IFN) alpha-2a monotherapy in a cohort of Chinese haemophilic patients co-infected with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) and undergoing highly active antiretroviral drugs therapy. Twenty-two (n = 22) patients with CD4 lymphocyte counts over 200 cells microL(-1) were treated with 180 microg of PEG-IFN alpha-2a subcutaneously once in a week for 48 weeks. HCV load (HCV RNA), HIV load (HIV RNA) and CD4 lymphocyte counts were measured at baseline and 4, 12, 24, 48 and 72 weeks after initiation of anti-HCV therapy. Efficacy and safety were analysed according to baseline CD4 status (> or =350 cells microL(-1)). Significant HCV-RNA decreases (>1 log(10) copies mL(-1)) were observed through week 72 after PEG-INF alpha-2a monotherapy across both CD4 strata. CD4 status was not associated with treatment outcomes as evaluated using rapid viral response rate (P = 0.655), early viral response rate (P = 0.387), end-of-treatment viral response rate (P = 1.000) or sustained viral response rate (SVR, P = 0.674). A sustained virological response was achieved in nine patients (41%), five with genotype 2a (83%) and four with genotype 1b (25%, P = 0.023). SVR was HCV genotype dependent. Eleven patients required a dose reduction in PEG-IFN alpha-2a. PEG-IFN alpha-2a monotherapy could be considered as a safe and effective option for the treatment of HCV infection in HIV patients with haemophilia, particularly in resource-limited settings. While higher CD4 lymphocyte counts resulted in greater HCV-RNA reduction, HCV genotype was a predictor for sustained virological response.
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PMID:Efficacy and safety of pegylated interferon alpha-2a therapy for chronic hepatitis C in HIV-infected patients with haemophilia. 2002 27


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