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)

Retinoic acid (RA) exerts potent suppressive and upregulatory effects on human immunodeficiency virus (HIV) expression in mononuclear phagocytes, strikingly similar to the effects of the cytokine transforming growth factor beta (TGF-beta). RA significantly inhibited phorbol ester-mediated, but not tumor necrosis factor alpha-mediated, induction of HIV transcription in the chronically infected promonocytic U1 cell line. RA and TGF-beta also completely suppressed the induction of virus production in U1 cells by interleukin 6 alone or in combination with glucocorticoids, which predominantly upregulate virus expression at the posttranscriptional level. Despite the close parallel to TGF-beta-induced effects, no evidence was obtained that RA mediated its effect by inducing secretion of active TGF-beta 1, -beta 2, or -beta 3. As with chronically infected U1 cells, similar inhibitory effects were also observed in primary monocyte-derived macrophages previously infected with HIV and then exposed to either RA or TGF-beta. In contrast, stimulation of monocyte-derived macrophages or U937 cells (the parental cell line of U1) with either RA or TGF-beta prior to in vitro infection resulted in the enhancement of virus production. Given the already successful use of retinoids in the treatment of several malignancies and the present demonstration of their capability of blocking the induction of HIV expression in infected mononuclear phagocytes, it would be of interest to pursue the potential role of this class of compounds in the development of strategies aimed at the pharmacologic regulation of HIV expression.
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PMID:Retinoic acid mimics transforming growth factor beta in the regulation of human immunodeficiency virus expression in monocytic cells. 137 88

Hairy leukoplakia was first described as an oral marker of human immunodeficiency virus infection in 1984. The clinical significance of this lesion in an otherwise healthy, high-risk symptom-free person is that it can be an early manifestation of human immunodeficiency virus infection. Because of its benign nature and the lack of clinical evidence that treatment of the lesion improves the prognosis of human immunodeficiency virus-infected patients, systemic therapy with antiviral drugs does not seem warranted at this time. Topical retinoids (Retin-A sol) and systemic antivirals such as acyclovir have been previously tried; however, lesions tend to recur a few days after treatment is discontinued. Nine patients with oral hairy leukoplakia seen at the Oral Medicine Clinic, University of California San Francisco were offered treatment with podophyllum resin 25% sol. All patients had a complete remission of their condition within 1 week (5 patients) or after the second application a week later (4 patients). Side effects were transient and reversible. These remissions of oral hairy leukoplakia lasted from 2 to 28 weeks, which suggests that podophyllum may be a relatively safe and cost-effective treatment of this otherwise symptom-free lesion.
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PMID:Retrospective findings of the clinical benefits of podophyllum resin 25% sol on hairy leukoplakia. Clinical results in nine patients. 151 42

Retinoic acid (RA) has been demonstrated to drive both phenotypic and functional in vitro differentiation of B cell hybridomas from patients with common variable immunodeficiency (CVI) who manifest an "intrinsic" defect in terminal B cell differentiation (J Exp Med 1988;168: 55-71). Therefore, we conducted an open trial to determine the effects of oral 13-cis RA (0.5 mg/kg/day; 12 weeks receiving and 12 weeks without drug) on in vivo B cell differentiation in subjects with CVI. At various times before, during, and after drug administration, patients' B cells were tested for changes in cell-surface phenotype and in vitro immunoglobulin production in response to recombinant cytokines. Before 13-cis RA, all patients had decreased Leu-8 coexpression on CD20+ cells. Seven of eight subjects demonstrated "normalization" of this phenotype after 8 to 16 weeks of 13-cis RA administration. Patients whose B cells demonstrated more than normal CD20 display also had a fall toward normal in this parameter. These effects persisted for 6 to 12 weeks after drug was stopped. It appears that 13-cis RA drives B cells of patients with CVI to express a more differentiated cell-surface phenotype and may promote functional differentiation in some patients.
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PMID:13-cis retinoic acid enhances in vivo B-lymphocyte differentiation in patients with common variable immunodeficiency. 172 Jan 49

Certain infections, like that with the human immunodeficiency virus-1, deplete vitamin A, and when vitamin A levels are low, immune dysfunctions establish susceptibility to further infection. Our research has focused on the immune dysfunctions that are a consequence of vitamin A deficiency and that predispose to further infection. We previously studied a helminth infection in mice, and showed that when vitamin A levels are low, the immune response develops a strong regulatory T cell imbalance with excessive T helper type-1 cell interferon (IFN)-gamma synthesis and insufficient T helper type-2 cell development and function. Here, we studied the T cell priming environment in vitamin A-deficient mice to learn how that priming environment might produce a regulatory T cell imbalance and consequently distort the ability of the immune system to respond to an infection. Our results show that during vitamin A deficiency, the priming environment included constitutive interleukin (IL)-12 and IFN-gamma transcripts, but it was devoid of constitutive IL-4 and IL-10 transcripts. Dietary all-trans-retinoic acid supplementation down-regulated the level of constitutive IL-12 and IFN-gamma transcripts. Furthermore, when T cells from naive vitamin A-deficient animals were stimulated through the T cell receptor, they produced excess IFN-gamma protein compared to T cells from control animals. In contrast, T cell stimulation failed to induce IL-4 or IL-10 secretion. The inducible IFN-gamma was largely from CD8+ T cells and all-trans-retinoic acid addition in vitro inhibited IFN-gamma production at the transcript level. Retinoic acid addition in vitro also decreased natural killer cell IFN-gamma synthesis at the transcript level. Taken together, the distorted constitutive and inducible cytokine gene expression patterns that occurred when vitamin A levels were low would be expected strongly to favor T helper type-1 development and limit T helper type-2 cell growth and differentiation, thereby limiting the animal's humoral immune response capability.
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PMID:Vitamin A deficiency results in a priming environment conducive for Th1 cell development. 761 95

A palindromic element (site B) located between bases -328 and -347 (relative to the start site of transcription) of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) was shown in a gel mobility shift assay to bind the human retinoic acid receptors (RARs). Greatly enhanced binding to this site was observed in the presence of both RAR and the retinoid X receptor. Retinoic acid responsiveness in F9 cells could be conferred on a thymidine kinase promoter by the presence of single or multiple copies of site B and responsiveness was abolished when this sequence was mutated to a form that could not bind RARs. However, the presence of this sequence did not render the HIV-1 LTR responsive to retinoic acid in F9 cells.
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PMID:A palindromic element in the human immunodeficiency virus long terminal repeat binds retinoic acid receptors and can confer retinoic acid responsiveness on a heterologous promoter. 838 9

Isotretinoin for acne vulgaris in the setting of chronic granulomatous disease (CGD) is a controversial therapeutic option. In this inherited immunodeficiency, inefficient tissue responses to bacteria and fungi lead to chronic and recurrent infections. Isotretinoin is known to be associated with several mucocutaneous side effects that could worsen the immune response in individuals with CGD. We report the fourth published case of acne vulgaris treated with isotretinoin in an individual with CGD, with a safe and successful outcome.
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PMID:Safe and successful treatment of acne vulgaris with isotretinoin in a patient with chronic granulomatous disease. 2196 49