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)

Serum samples of 120 patients in different stages of chronic human immunodeficiency virus type 1 (HIV-1) infection, 11 patients with primary HIV-1 infection (PHI), and 49 HIV-1 seronegative homosexual men were analyzed for tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), and HIV-1 p24 antigen. Increased levels of IFN-alpha and TNF-alpha were found in some, but not all, cases with PHI. During progressing disease IFN-alpha occurred in serum with increasing frequency and concentration. Raised levels of TNF-alpha were found in all stages of chronic infection, but were less common in patients with AIDS than were raised levels of IFN-alpha. The levels of the two substances were not correlated. There was a correlation between IFN-alpha, but not TNF-alpha, and the occurrence of HIV-1 p24 antigen in serum. These results suggest that IFN-alpha and TNF-alpha are induced by different agents during HIV-1 infection. The findings would be consistent with the hypothesis that IFN-alpha and TNF-alpha are counteracting forces that have important down- and upregulatory effects, respectively, on HIV-1 replication in vivo.
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PMID:Interferon-alpha and tumor necrosis factor-alpha in serum of patients in various stages of HIV-1 infection. 190 89

Chronic liver disease associated with hepatitis C virus (HCV) is an important cause of morbidity and mortality in hemophilia. We have used recombinant interferon alpha-2b (IFN alpha-2b) in a randomized controlled liver biopsy trial to treat hemophiliacs with chronic hepatitis. Eighteen patients entered the study, 16 of whom were subsequently shown to have antibodies to the HCV. All underwent liver biopsy at entry and were randomized to either treatment with self-administered IFN alpha-2b, 3 million units subcutaneously thrice weekly (n = 10) or no treatment (control group) (n = 8). Nine subjects had chronic active hepatitis, seven had chronic persistent hepatitis, and two had cirrhosis. Twelve months after entry into the study 17 patients underwent a second liver biopsy. All biopsies were coded, assessed, and scored according to the histologic severity of the liver disease. Ten patients were administered IFN for 1 year, and in four patients normalization of alanine aminotransferase (ALT) occurred compared with none in the untreated group. After the second liver biopsy, six of the eight initial no-treatment patients were treated with interferon 3 million units thrice weekly for 6 months, and normalization of ALT was seen in five patients. Biochemical relapse within 4 months of stopping IFN occurred in one of four patients treated for 1 year and in four of five patients treated for 6 months. IFN treatment was well tolerated. Although the histologic scores of the two groups were similar at entry into the study, after 12 months the biopsy appearances in the treated group were significantly improved compared with the controls (P less than .01). Histologic improvement was noted in the three interferon-treated human immunodeficiency virus antibody-positive patients and also in other patients who had no biochemical response. We conclude that low-dose recombinant IFN alpha is effective in normalizing transaminases and improving the histologic appearances in at least 50% of hemophiliacs with chronic hepatitis C.
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PMID:A randomized controlled trial of recombinant interferon-alpha in chronic hepatitis C in hemophiliacs. 191 56

alpha-Interferon (IFN alpha) blocks replication of human immunodeficiency virus (HIV)-1 in vitro by interfering with the release of mature virions. Clinical trials have addressed the in vivo effects of IFN alpha, both alone and in combination with other agents, in a variety of patients at all stages of HIV-1 infection. Patients with late stages of HIV-1 infection (CD4 counts under 100) show few positive results following treatment with IFN alpha. Patients with earlier stages of HIV infection, however, may benefit from treatment with this agent. Several clinical trials have demonstrated the activity of interferon in the treatment of patients with acquired immunodeficiency syndrome, Kaposi's sarcoma, and CD4 counts over 200. In these trials, response rates of approximately 40% have been reported, with the probability of response directly correlated with the level of CD4 cells. These antitumor effects have been associated with declines in the circulating levels of the HIV-1 core antigen p24. alpha-Interferon activity has also been studied in patients concomitantly receiving zidovudine. In these studies, neutropenia, reversible with the concomitant administration of granulocyte macrophage colony-stimulating factor, has been the most common dose-limiting toxicity. Both the antitumor and antiviral activities of combination therapy appear to be at least as good as those observed when single agents are used. Controlled clinical trials are currently under way to evaluate the role of interferon therapy, both alone and in combination with zidovudine, in patients with early HIV infection.
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PMID:The role of alpha-interferon in patients with human immunodeficiency virus infection. 194 29

AZT inhibited replication of an immunodeficiency-inducing strain of feline leukemia virus (FeLV-FAIDS) in vitro at concentrations as low as 0.005 microgram/mL. This antiviral activity was augmented an additional 25-30% when AZT was combined with human recombinant alpha-interferon (2b) (IFN alpha). Administration of AZT alone or in combination with IFN alpha, beginning at the time of exposure to a 100% persistent viremia-inducing dose of FeLV-FAIDS, abrogated the progression of viral infection and protected treated animals from induction of persistent antigenemia and disease. Low levels of antigenemia were detected intermittently in some AZT-treated cats throughout the 6 week treatment and 40 week observation period. Combination of AZT with IFN alpha appeared even more effective than AZT alone. In this treatment group even transient antigenemia was undetectable throughout the therapy and posttherapy observation periods, and latent virus could not be reactivated from bone marrow cells of protected animals. These results provide additional evidence that early treatment with AZT or AZT/IFN alpha therapy can be effective in completely aborting retroviral infections.
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PMID:Therapy of presymptomatic FeLV-induced immunodeficiency syndrome with AZT in combination with alpha interferon. 196 30

Human recombinant interferon-alpha (IFN alpha) restricted viral replication in human immunodeficiency virus- (HIV) infected T cells and monocytes. With T cells, reverse transcriptase (RT) activity in culture fluids was reduced threefold from that of control infected cells by IFN treatment, but HIV p24 antigen levels were unchanged. In contrast, levels of p24 antigen and RT activity in lysates of IFN-treated infected cells were threefold greater than those of controls. These differences suggest that the mechanism for IFN-induced antiviral effects in HIV-infected T cells resides in the terminal events (assembly and release) of the virus replication cycle. Monocytes treated with IFN at the time of virus challenge showed no p24 antigen or RT activity, no HIV-specific mRNA, and no proviral DNA in cells for up to 3 weeks after infection. IFN treatment of chronically infected monocytes also decreased virus replication, as assessed by p24 antigen, mRNA and RT detection assays. However, levels of proviral DNA in the IFN-treated and control HIV-infected cells were indistinguishable. The presence of large quantities of proviral DNA in cells with little or no evidence for active transcription documents a situation approaching true microbiological latency.
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PMID:Restriction of HIV replication in infected T cells and monocytes by interferon-alpha. 212 Nov 92

Zidovudine (3'-azido-3'-deoxythymidine; AZT) inhibited replication of an immunodeficiency-inducing strain of feline leukemia virus (FeLV-FAIDS) in vitro at concentrations of 0.5-0.005 micrograms/ml. A 25-30% additional antiviral effect was achieved in vitro when AZT was combined with human recombinant alpha interferon 2a (IFN alpha). Oral administration of AZT (20 mg/kg three times daily) to cats resulted in plasma concentrations of 3 micrograms/ml at 2 h post-administration with a T1/2 of approximately 1.60 h. Administration of AZT alone or in combination with IFN alpha or interleukin-2 (IL-2) throughout a 6-week treatment period enabled cats to resist challenge with FeLV-FAIDS. In contrast, those cats treated with IFN alpha or IL-2 alone became persistently antigenemic (core protein p27) in parallel with placebo-treated controls. Antigenemia remained undetectable in AZT-treated cats throughout an 80-day period post-inoculation (38 days after treatment was withdrawn). However, latent FeLV-FAIDS in bone marrow was detectable by in vitro culture of progenitor cells in the presence of hydrocortisone. Serial analysis of circulating p27 antigen, neutralizing antibody, and quantification of latent, reactivatable virus indicated that those animals receiving AZT in combination with IFN alpha were most able to resist FeLV-FAIDS challenge. This work provides additional evidence that early presymptomatic treatment employing combination chemoimmunotherapy can be effective in medical intervention of retroviral infection.
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PMID:Zidovudine in combination with alpha interferon and interleukin-2 as prophylactic therapy for FeLV-induced immunodeficiency syndrome (FeLV-FAIDS). 216 83

The effect of interferon-alpha (IFN-alpha) on virus replication in cells acutely infected with human immunodeficiency virus type 1 (HIV-1) and virus production from cells persistently infected with HIV-1 was studied. In both cell systems, significant suppression was observed. However, this suppression was not due to protein synthesis of the major viral proteins. Electron microscopy revealed the accumulation of intact virus particles on the cell surface of the cells treated with IFN-alpha. Thus, IFN-alpha might suppress the release stage of the particle from infected cells.
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PMID:Interferon-alpha treatment leads to accumulation of virus particles on the surface of cells persistently infected with the human immunodeficiency virus type 1. 221 6

A sensitive and quantitative focal immunoassay has been used to measure the effects of three different therapeutic agents on tissue culture cells infected with human immunodeficiency virus (HIV). The effects of the drugs were studied on both acutely and persistently infected CD4+ cell lines. The three agents, azidothymidine (AZT), interferon-alpha (IFN-alpha), and an anti-HIV envelope antibody coupled to ricin A chain, were tested alone and in combination. AZT was found to have its greatest effect during early stages of the infection, but also had an action on persistently infected T cell lines. The effect of AZT on persistently infected cells was seen within 24 h, increased with extended exposure to the drug, and persisted after its removal. IFN-alpha had variable effects on acutely infected cells but suppressed chronic infection. Combinations of the therapeutic agents were studied. Using a model that allowed for treatment during both acute and persistent stages of infection, the most effective combination in suppressing HIV infection was the continual use of both AZT and IFN-alpha at the highest tolerable doses. Knowledge of the efficacy of AZT on persistently infected cells will allow for the most effective design of clinical protocols.
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PMID:AZT demonstrates anti-HIV-1 activity in persistently infected cell lines: implications for combination chemotherapy and immunotherapy. 223 Feb 56

A promonocytic cell model was used to investigate cytokine gene transcription in U937 and U9-IIIB cells chronically infected with human immunodeficiency virus type 1 (HIV-1). The production of interferon (alpha-1 interferon [IFN-alpha 1], IFN-alpha 2, and IFN-beta), interleukin (interleukin 1 alpha [IL-1 alpha], IL-1 beta, and IL-6), and tumor necrosis factor alpha (TNF-alpha) mRNA was characterized by quantitative polymerase chain reaction mRNA phenotyping in U937 and U9-IIIB cells following coinfection with Sendai paramyxovirus or stimulation with lipopolysaccharide (LPS). Chronic HIV-1 infection of U9-IIIB cells resulted in a low constitutive level of transcription of TNF and IL-1 genes but not IFN genes; however, when the cells were coinfected with Sendai virus, 10- to 20-fold higher levels of IFN-beta, IL-1 beta, IL-6, and TNF-alpha mRNA were observed in U9-IIIB cells than in similarly induced U937 cells. The enhanced levels of cytokine RNA in virus-infected U9-IIIB cells were also accompanied by higher levels of IFN antiviral activity and TNF secretion than in U937 cells. Transcript levels for IFN-alpha 1 and IFN-alpha 2 were equivalently induced in virus-infected U937 and U9-IIIB cells, indicating that a generalized derepression of cytokine gene expression did not occur as a consequence of HIV-1 infection. When LPS was used as an inducer, a distinct pattern of cytokine gene expression was detected in U9-IIIB cells. TNF-alpha and IL-1 beta but not IFN-alpha or IFN-beta transcripts were induced by LPS. These results suggest that HIV-1 infection of promonocytic cells may prime or sensitize cells such that subsequent antigenic challenge leads to coordinate enhancement of cytokine gene expression.
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PMID:Coordinate enhancement of cytokine gene expression in human immunodeficiency virus type 1-infected promonocytic cells. 224 88

Interferon alpha (IFN-alpha) induces significant antiretroviral activities that affect the ability of human immunodeficiency virus (HIV) to infect and replicate in its principal target cells, CD4+ T cells and macrophages. A major endogenous source of IFN-alpha during any infection is the macrophage. Thus, macrophages have the potential to produce both IFN-alpha and HIV. In this study, we examined the production of IFN-alpha and other cytokines by macrophage colony-stimulating factor (M-CSF)-treated cultured monocytes during HIV infection. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, IFN-omega, or IFN-beta were not detected nor was the mRNA expressed in either uninfected or HIV-infected monocytes. However, both uninfected and HIV-infected monocytes produced high levels of each of these cytokines after treatment with synthetic double-stranded RNA [poly(I).poly(C)]. Uninfected monocytes also produced high levels of IFN-alpha after treatment with poly(I).poly(C), Newcastle disease virus, or herpes simplex virus. In marked contrast to the preceding observations, HIV-infected monocytes produced little or no IFN-alpha before or after treatment with any of these agents. The absence of detectable IFN-alpha activity and mRNA in poly(I).poly(C)-treated HIV-infected monocytes was coincident with high levels of 2',5' oligoadenylate synthetase and complete ablation of HIV gene expression. The antiviral activity induced by poly(I).poly(C) may be a direct effect of this synthetic double-stranded RNA or secondary to the low levels of IFN-beta and IFN-omega produced by infected cells. The markedly diminished capacity of HIV-infected monocytes to produce IFN-alpha may reflect a specific adaptive mechanism of virus to alter basic microbicidal functions of this cell. The inevitable result of this HIV-induced cytokine dysregulation is virus replication and persistence in mononuclear phagocytes.
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PMID:A selective defect of interferon alpha production in human immunodeficiency virus-infected monocytes. 198 24


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