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 immune system is regulated by soluble glycoproteins produced by a wide variety of cells. IL-10 is a soluble protein produced by helper T (Th) cells, macrophages (M phi)/monocytes (Mo), and B cells, which exhibits a wide array of both immunosuppressive and immunostimulatory properties. We examined the pathological significance of this new cytokine "IL-10", and its clinical implications. IL-10 was discovered in 1989 as an activity produced by murine type 2Th (Th2) cells which suppressed cytokine production such as interferon gamma (IFN gamma) by type 1Th (Th1) cells. Its inhibitory effects were mainly recognized in vivo in animal experiments. In humans, unlike in mice, it is difficult to separate Th1 from Th2 cells. However, as we expected, marked suppressive activities on M phi/Mo were observed in humans. We have examined the serum levels of IL-10 in several diseases. In autoimmune diseases, some of the patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) had higher titers of IL-10 in their sera than the normal controls. Conversely, some patients with common variable immunodeficiency and with inflammatory bowel diseases showed lower titers of IL-10 in their sera than the healthy controls. Most bacterial endotoxin shock patients had lower levels of serum IL-10 than cardiogenic shock patients. Collectively, the ability of IL-10 to suppress the production of inflammatory monokines and to elevate anti-inflammatory monokines, suggests a strong anti-inflammatory role in diseases such as septic endotoxin shock and inflammatory bowel diseases. Also, the IL-10 antagonist such as soluble IL-10 receptor might be a candidate for the treatment of B cell mediated autoimmune diseases such as SLE by selectively enhancing Th1 immunity.
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PMID:[Clinical implication of IL-10 in patients with immune and inflammatory diseases]. 793 21

In humans with advanced human immunodeficiency virus (HIV) infection, an interferon-alpha (IFN-alpha) response by a specialized blood mononuclear cell to herpes simplex virus (HSV) in vitro is associated with resistance to opportunistic infections. A cell type of unknown lineage, designated the natural IFN-producing cell (NIPC), has been identified preliminarily as the source of these IFNs and may have a role in other host defense functions. Earlier studies suggested the existence of analogous HSV-responsive cell populations in mice. The role specifically of IFN-alpha in the murine system, however, has not been characterized. Using IFN bioassay and neutralization with antisera against Type I IFNs and IFN-beta, we have defined the types and sources of IFNs produced by mice in response to in vivo and in vitro challenge with UV-inactivated HSV. After intraperitoneal inoculation with HSV, BALB/c and C57Bl/6 strains produced characteristically different levels of serum IFNs that appeared principally to be IFN-alpha. The response of mononuclear cells from these mice differed from that of the intact mouse. Isolated cells from bone marrow and spleen released detectable IFNs much later than did whole animals, and the IFNs produced by marrow, spleen, and peritoneal cells were usually neutralized by the anti-IFN-beta. Only bone marrow cells produced detectable amounts of IFN-alpha. Both intact mice and their cells became refractory to restimulation with similar kinetics.
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PMID:Interferon-alpha generation in mice responding to challenge with UV-inactivated herpes simplex virus. 802 90

Monocytes treated with 500 IU/ml human recombinant interferon-gamma (rIFN-gamma) 1 day before and continuously after human immunodeficiency virus (HIV) infection showed no evidence of virus replication 7 days after addition of the viral inoculum. There was no HIV-associated cytopathic effect, no reverse transcriptase (RT) activity or p24 detected in culture fluids, and no HIV RNA or DNA in cell lysates. Furthermore, no evidence of HIV infection was evident in replicate cultures in which all IFN-gamma was removed at 7 days and the cells were cultured for an additional 3 weeks without IFN-gamma. The 50% inhibitory dose for reduction of maximum RT activity in HIV-infected monocyte cultures was about 1 IU/ml IFN-gamma. No increase in HIV replication was evident in monocytes treated with IFN-gamma at any concentration (0 to 5000 IU/ml) or at any time (7 days before to 10 days after HIV infection). In side-by-side experiments with identical monocytes and HIV-1 stock, rIFN-gamma was 10 to 20 times more effective than rIFN-alpha 2b for induction of antiviral activity. With both interferons, significant antiviral activity was evident with monocytes treated 1 day before, at the time of, or up to 3 days after infection. At 7 to 10 days after infection (a time at which less than 20% of total cells were infected with HIV) addition of even high concentrations of IFN-alpha or IFN-gamma had no effect on virus replication. These data suggest that the principal action of IFN-alpha and IFN-gamma was directed against the fluid-phase virus. Cell-cell spread of infection within the HIV-infected monocyte culture and extent of virus replication in HIV-infected cells were not affected by interferon treatment.
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PMID:Interferon-gamma protects primary monocytes against infection with human immunodeficiency virus type 1. 808 9

The human peripheral blood mononuclear cells responsible for IFN-alpha production in response to viral stimuli have been most often described as either monocytes (as typified by the response to Sendai virus) or as a light density, HLA-DR+ population which is negative for most cell surface markers characteristic of mature T cells, B cells, monocytes, or natural killer cells (as typified by the response to Herpes simplex virus (HSV)). The frequency of IFN-alpha-producing cells (IPC) responding to Sendai virus is typically 10-fold or more higher than those responding to HSV. In the current study, we have used ELISpot assays to determine the frequency of IPC responding to DNA and RNA viruses including HSV, Sendai, vesicular stomatitis virus, cytomegalovirus, adenovirus, SV40, influenza, measles, mumps, Newcastle disease virus (NDV) and human immunodeficiency virus (HIV). The enveloped viruses but not the nonenveloped viruses (adenovirus and SV40) elicited an IFN-alpha response. The frequency of IPC for each of the other viruses was more similar to the low frequency HSV-responding population than to the higher frequency Sendai virus response. These included several viruses in the same family as Sendai virus, namely the paramyxo viruses measles, mumps, and NDV. IPC were also tested for sensitivity to the lysosomotropic drug chloroquine, which diminishes IFN-alpha produced in response to HSV but not Sendai virus. With the exception of Sendai virus, chloroquine treatment abrogated the majority of IFN-alpha produced and IPC against each of the viruses. We conclude that low frequency, nonmonocytic NIPC account for the majority of IFN-alpha production in response to different viruses.
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PMID:Viral induction of low frequency interferon-alpha producing cells. 809 44

We report the case of a young hemophilic patient with antibodies against the human immunodeficiency virus (HIV) who was affected by immune thrombocytopenic purpura (ITP). This condition did not respond to pharmacological therapy with steroids and alpha-2b-r-IFN, and the patient was splenectomized. Immune status evaluation was performed before and after surgery and during follow-up with CD4-CD8 monoclonal antibodies and cytofluorimetric analysis in order to explore possible correlations between splenectomy and the cytologic immune regulatory system. Splenectomy resulted in a resolution of ITP with consequent disappearance of the hemorrhagic diathesis related to thrombocytopenia. Moreover, at 30 months from splenectomy the patient is still in remission, his CD4 count is not decreased, and no progression to AIDS has been evidenced. These aspects are analyzed and briefly discussed.
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PMID:Splenectomy outcome in a hemophilic patient with HIV-related immune thrombocytopenia. 809 12

In vitro cultivated human monocytes show a time-dependent differentiation into macrophages, characterized by an increased expression of macrophage-specific antigens. Monocytes-macrophages were infected with human immunodeficiency virus type 1 strain Ba-L (HIV-1Ba-L) at different stages of differentiation. When 7-day cultured macrophages were infected in the presence of antibodies to beta interferon (IFN-beta), a significant increase in HIV-1 p24 release was detected. This effect was not observed in 1-day monocytes. This finding suggests that IFN-beta secreted by the infected macrophages inhibits p24 release. Treatment of cultured macrophages with recombinant gp120 (rgp120) protein resulted in the induction of IFN-beta mRNA and in an antiviral state to vesicular stomatitis virus. This rgp120-induced antiviral state was largely neutralized by antibodies to IFN-beta, whereas anti-IFN-alpha antibodies were ineffective. In cultured macrophages, 0.1 IU of IFN-beta per ml was sufficient to induce a marked inhibition of vesicular stomatitis virus yield, whereas this dose was ineffective in 1-day monocytes. These results indicate that (i) HIV-1 (possibly in part through its gp120 protein) induces low levels of IFN-beta in macrophages and (ii) this IFN-beta is very effective in inducing an antiviral state in differentiated macrophages.
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PMID:Induction of beta interferon by human immunodeficiency virus type 1 and its gp120 protein in human monocytes-macrophages: role of beta interferon in restriction of virus replication. 810 59

A tumour-associated antigen known as 90K has been found in high concentrations in the serum of patients infected with human immunodeficiency virus (HIV) even in the absence of neoplastic complications. In order to investigate the relationship between the production of 90K and soluble inflammatory mediators, we studied serum concentrations of the antigen, tumour necrosis factor-alpha (TNF-alpha), interleukin-I-alpha (IL-I-alpha), interferon-gamma (IFN-gamma), IFN-alpha, neopterin and beta 2-microglobulin (beta 2-m) in patients with non-neoplastic HIV infection at various stages of disease and in control persons. The antigen was detected in all those studied but its concentration was higher in HIV-infected patients compared with controls (P < 0.001), increasing progressively with advancing stages of disease. There was a negative correlation between concentrations of 90K and IL-I-alpha in patients in U.S.A. Centers for Disease Control groups II and III (P < 0.02) and also between that of 90K and both TNF-alpha (P < 0.01) and IL-I-alpha (P < 0.05) in control persons. The results indicate that 90K is not merely a tumour-associated antigen and that its production may be part of immune and inflammatory responses in the absence of neoplasia. The correlation between the concentrations of 90K and of some cytokines in asymptomatic patients and healthy persons suggests that 90K may be part of a network of immune and inflammatory reactants.
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PMID:Relationship between the tumour-associated antigen 90K and cytokines in the circulation of persons infected with human immunodeficiency virus. 816 31

EBVirus-associated B cell lymphoproliferative disorder (BLPD) is a recognized complication of primary immunodeficiency and organ as well as bone marrow transplantation. Although the nature of the immune defects that predispose to the development of BLPD are unknown, it is postulated that aberrant T cell responses are involved. It is our hypothesis that unbalanced lymphokine production is a major contributory factor to abnormal B cell growth in response to EBV, resulting in BLPD. Since IFN-alpha and IL-4 are important regulators of B cell proliferation and also regulate the synthesis of IgE, we determined serum levels of IFN-alpha, IL-4, and IgE in 8 patients with newly diagnosed BLPD. Comparison was made to healthy recipients of organ transplants on immunosuppressive therapy without BLPD, and normal EBV seropositive controls. Levels of serum IL-4 were significantly elevated in both patients with BLPD as well as in healthy immunosuppressed organ transplant recipients as compared with normal healthy individuals. Patients with BLPD exhibited a combination of significantly lower levels of serum IFN-alpha, and significantly higher levels of serum IgE than either healthy EBV seropositive individuals or healthy recipients of organ transplants on immunosuppressive therapy. These results suggest that imbalance in the proportions of circulating cytokines favoring B cell proliferation may be contributing to the development of EBV-associated BLPD. The potential significance of the finding of low IFN-alpha in patients who develop BLPD is exemplified by our recent success in the treatment of BLPD with IFN-alpha and intravenous IgG.
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PMID:Immunoregulatory abnormalities in patients with Epstein-Barr virus-associated B cell lymphoproliferative disorders. 816

Defective T cell activation has been recognized in a number of patients with primary immunodeficiencies (ID). A distal defect resulting in abnormal production of IL2, IL3, IL4 and IFN gamma was found to be associated with reduced binding of the NF-AT transcription factor to the promoters of the genes coding for these lymphokines. Defect in early steps of T cell activation have been described in primary IDs, consisting in defective calcium flux and phosphoinositides turnover following TCR/CD3 ligation. We herein report a primary ID found in a 13 year old girl. It consists in a partially defective T cell proliferation which could be related to a defective Tyrosine phosphorylation.
Immunodeficiency 1993
PMID:Functional T cell immunodeficiency characterized by defective TCR/CD3 induced tyrosylphosphorylation. 816 86

Deficient in vitro production of interferon-alpha (IFN-alpha) in response to herpes simplex virus (HSV) occurs in patients infected with the human immunodeficiency virus (HIV), with the most deficient responses associated with opportunistic infections (OI). The peripheral blood mononuclear cells (PBMC) which produce IFN-alpha in response to HSV are light density, HLA-DR+ cells lacking any unique surface markers and have been termed "natural interferon-producing cells" (NIPC). In this study, IFN-alpha responses were measured and the ELISpot assay was utilized to determine the frequency of NIPC in response to HSV. As expected, HIV-infected patients had depressed IFN-alpha production. In the ELISpot assay, healthy controls had a mean frequency of 1:703 NIPC among PBMC; each NIPC made approximately 2 international units (IU) of IFN-alpha. HIV-infected patients on average had fourfold less NIPC than controls and produced 1 IU IFN-alpha/NIPC; the plaque size for patient samples was often smaller than that for controls. NIPC frequency and IFN-alpha production were lowest in patients with a history of OI. In conclusion, deficient IFN-alpha production by AIDS patients results from reductions in both the frequency and the activity of NIPC, probably reflecting a gradual turning off of IFN-alpha production.
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PMID:Decreased frequency of functional natural interferon-producing cells in peripheral blood of patients with the acquired immune deficiency syndrome. 818 Nov 90


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