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At least 289 records · Page 16Linked to original sources
PubMed2003

Immune reconstitution in HIV infection and its relationship to cancer.

HIV infection results in formidable immune dysfunction, widely affecting the immune system, but typified by T lymphopenia. This dysfunction includes a perturbed immune response to several persistent viruses that have a propensity to cause tumors. Effective control of HIV replication by highly active antiretroviral therapy (HAART) results in regeneration of the damaged immune system, and recent advances have allowed this immune reconstitution to be better defined. This article describes the immunodeficiency caused by HIV and the response of the immune system to HAART, with specific reference to the immune response to cancers associated with HIV infection.

HIV Infections↗
PubMed1995

Vitamin A deficiency results in a priming environment conducive for Th1 cell development.

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.

Animals↗
PubMed1996

Melatonin administration following hemorrhagic shock decreases mortality from subsequent septic challenge.

Melatonin administration has been reported to have beneficial effects on immune function in some clinical studies and in several animal models of immune dysfunction. Furthermore, recent studies suggest beneficial effects of melatonin on depressed immune function following trauma-hemorrhage. Nonetheless, it remains unknown whether this hormone has any salutary effects on survival following hemorrhagic shock and subsequent septic challenge. Male C3H/HeN mice were bled to and maintained at a mean arterial blood pressure of 35 +/- 5 mm Hg for 90 min, adequately resuscitated, and 48 hr thereafter subjected to sepsis (cecal ligation and puncture; CLP). Melatonin-treated mice received either short-term treatment on Days 1 and 2 after hemorrhage or continuous treatment throughout the study. Treatment with vehicle (10% ethanol in normal saline) or melatonin (10 mg/kg body weight) was administered daily starting in the evening of the day of hemorrhage/sham-operation. Short-term melatonin administration after hemorrhage significantly improved survival in animals subjected to septic challenge. Continuous melatonin treatment did not improve survival, as compared to vehicle-treated mice subjected to shock and CLP. Moreover, continuous melatonin treatment in sham-operated animals significantly increased mortality compared to short-term-treated and vehicle-treated animals. While the mechanisms of the differential effects of melatonin administration are yet to be clearly defined, this study, nonetheless, demonstrates the salutary effects of short-term melatonin administration in the treatment of immune dysfunction following hemorrhagic shock.

Animals↗
PubMed1996

Monocyte and blood interleukin-12 levels in patients with obstructive jaundice.

Patients with obstructive jaundice have an increased incidence of peri-operative complications and immune dysfunction. This study was to investigate interleukin (IL)-12 (a cellular immunity stimulant), levels in jaundiced patients. 23 jaundiced patients and 17 controls were studied. There was significantly increased monocyte IL-12 production in jaundice, as measured by an ELISA, compared with that in controls (p < 0.01 by Mann-Whitney U test). A similar increase is seen in both benign and malignant jaundice. There was no difference between plasma IL-12 levels in the two groups. It is concluded that in jaundice, monocytes have a significantly increased capacity to release IL-12. This suggests that IL-12 may play a role in the immune dysfunction in jaundiced patients.

Cholestasis↗
PubMedDate not supplied

Fungal infections in the immunocompromised host.

With the increased number of immunocompromised patients there has been a concomitant increase in patient morbidity and mortality due to fungi. The etiologic microorganisms vary depending upon the type of immune dysfunction. Patients with malignancies and chemotherapy-induced neutropenia commonly are infected with Candida and Aspergillus. Other ubiquitous fungi such as Rhizopus, Fusarium, and Trichosporon are more frequently implicated as agents of disease in these patients. Patients with cell-mediated immune dysfunction such as acquired immune deficiency syndrome (AIDS) are susceptible to mucocutaneous candidiasis and pulmonary and disseminated cryptococcosis. Histoplasmosis and coccidioidomycosis have been particularly lethal infections in AIDS patients. Contributing factors such as broad-spectrum antibiotic use, intravenous catheterization, malnutrition, hyperalimentation, multiple surgical procedures and/or trauma, and steroids used either singly or in combination may also predispose patients to invasive fungal disease. Definitive diagnosis is often difficult to establish and usually requires invasive biopsy. Delay of culture results due to the time required to process specimens and to allow the fungus to grow also contributes to the poor results of therapy. Biopsy of skin lesions represents a useful technique for making a diagnosis. Recent advances in antifungal therapeutics promise to change the current approach to treatment for several of the mycoses. The availability of new oral azoles with spectra of activity that include aspergillosis and cryptococcosis, which currently require treatment with parenteral amphotericin B, may prove practical for prolonged oral therapy of otherwise lethal mycoses.

Antifungal Agents↗
PubMedDate not supplied

Heterogeneity of immune markers in hemophagocytic lymphohistiocytosis: comparative study of 9 familial and 14 familial inheritance-unproved cases.

PURPOSE: Although immune dysfunction is suspected in patients with hemophagocytic lymphohistiocytosis (HLH), the difference between immune dysfunction in patients with familial erythrophagocytic lymphohistiocytosis (FEL) and familial inheritance-unproved lymphohistiocytosis (FIU) remains unknown. The aim of this study was to determine useful markers to distinguish patients with FEL from those with FIU. PATIENTS AND METHODS: Clinical features and laboratory findings, especially natural killer (NK) cell activity and the relative frequencies of peripheral blood mononuclear cell (PBMC) subsets, and serum levels of interferon-gamma and soluble interleukin-2 receptor were compared in 9 patients with FEL and 14 age-matched patients with FIU. Twenty-seven healthy infants served as controls. The treatment and outcome were also compared for patients with FEL and FIU. RESULTS: Comparison between patients with FEL and FIU revealed significantly lower NK activity in those with FEL (p = 0.03) but failed to show any significant differences in PBMC subsets, except that the percentage of CD3+ T cells was higher in patients with FEL (p = 0.02). CD4- and CD8-dominant phenotypes were characteristic findings in both groups of patients, although increased CD19+ B cells were restricted to patients with FIU. NK activity was deficient (< 5%) in four of the seven patients with FEL tested but in only one of eight patients with FIU. By comparison to values for age-matched controls, the percentages of CD3+, CD3+DR+ and CD45RO+ PBMCs in patients with FEL were significantly high (p < 0.05) and those of CD19+ and CD45RA+ subsets were lower than normal. Among patients with FIU, PBMC subsets included significantly reduced CD3+, CD4+, CD45RA+, and CD4+CD45RA+. In this small series, the outcome of patients with FEL and FIU treated with chemotherapy was not significantly different at the time of evaluation. CONCLUSIONS: These results indicate considerable immune heterogeneity among patients with HLH younger than 2 years. Although NK activity was useful but not diagnostic, determination of PBMC subsets and patterns of cytokine expression was not helpful in distinguishing patients with FEL from those with FIU, suggesting that the immune responses characteristic of these diseases may reflect different triggering factors, including viruses. The impact of this immune heterogeneity on patients' outcome remains to be determined.

Antigens, CD↗
PubMed1996

Inhibition of T and B cell proliferation by titanium, cobalt, and chromium: role of IL-2 and IL-6.

The mechanism by which an increased risk of prosthetic infection is induced in patients with total joint arthroplasties is poorly understood. The adverse effects of metallic corrosion products of a prosthesis on host defense mechanisms, particularly immune response and release of immunoregulatory cytokines, remain largely unknown. Titanium, cobalt, and chromium are the materials most often used for joint implantation. Therefore, this study was aimed at investigating the cytotoxicity of titanium, cobalt, and chromium and whether these metals affect T and B cell proliferation and the release of cytokines by human peripheral blood mononuclear cells (PBMC) in vitro. Metal cytotoxicity was not observed judging by cell viability and cell injury after PBMC was extensively exposed to the metals. Phytohemagglutinin (PHA)-induced T cell proliferation and lipopolysaccharide-induced B cell proliferation were significantly inhibited by titanium, chromium, and cobalt. The release of IL-2 and IL-6 by PHA-stimulated PBMC was significantly inhibited by titanium, chromium, and cobalt. Titanium did not alter IFN-gamma production, whereas chromium and cobalt significantly reduced IFN-gamma release by PHA-stimulated PBMC. The addition of IL-2 and IL-6 significantly restored the metal-induced inhibition of T cell and B cell proliferation, respectively. This study sheds light on how the metals impair immune response and cytokine release, suggesting that patients with an extensive exposure to the metals may develop immune dysfunctions. The compromised immune response induced by the metals might significantly contribute to an increased risk of infection in patients with joint prostheses.

B-Lymphocytes↗
PubMed1991

External ocular herpesvirus infections in immunodeficiency.

Infections of the eye with members of the herpes family of viruses (e.g. HSV, CMV, VZV) are frequent manifestations of acquired and inherited defects in cell mediated immunity. Herpesvirus infections in the immunocompromised may reflect frequent viral reactivation from the latent state, as well as extensive productive infection of ocular structures following reactivation or primary infection. A review of experimental and clinical studies of both acquired and inherited immune dysfunction implicates specific immune mechanisms influencing the establishment of latency, viral reactivation and the control of active viral replication in ocular tissues.

Herpes Zoster↗
PubMed1996

Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis, and adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) and human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with differing patterns of immune dysfunction. Biomarkers of immune activation may correlate with perturbations of immune function associated with these diseases. We conducted a pilot cross-sectional study to assess four candidate biomarkers of immune activation. beta 2-microglobulin, neopterin, tryptophan, and kynurenine levels were assayed in stored sera from asymptomatic, human T-cell leukemia virus type I (HTL V-I)-seronegative (HTLV-I-) and HTLV-I-seropositive (HTLV-I+) individuals, and ATL and HAM/TSP patients previously enrolled in seroepidemiological studies in Jamaica. Mean levels of beta 2-microglobulin, neopterin, and kynurenine were significantly elevated among ATL patients compared to the other study groups. Mean tryptophan levels were significantly lower among ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups. No significant differences in biomarkers were found between the HTLV-I- and HTLV-I+ groups. Among HAM/TSP patients, a significant association was found between elevated neopterin levels and symptoms of less than 4 years duration. In Cox proportional hazards regression modeling, neopterin and tryptophan were found to be independent predictors of survival among ATL patients. This study demonstrates a differential pattern of biomarkers of immune activation among ATL and HAM/TSP patients compared to HTLV-I- and HTLV-I+ individuals. Neopterin and tryptophan may be useful clinical indicators of disease severity and prognosis among HAM/TSP and ATL patients.

Adult↗
PubMed1993

Activation of alveolar macrophages in asymptomatic HIV-infected individuals.

After the initial infection with HIV, there is evidence of immune dysfunction despite an apparent normal clinical state. In the context that the lung is a major site affected by opportunistic infection during the progression of this immune dysfunction, and that some components of the immune system are activated during early HIV infection, we hypothesized that there may be activation of alveolar macrophages (AM), a key component of the pulmonary host defense system, during the asymptomatic phase of HIV infection. Compared to normals, in HIV-infected individuals the class II MHC molecules DR, DQ, and DP were all expressed more frequently and in greater cell surface density on AM (p < 0.03, all comparisons), and there was increased spontaneous release of superoxide anion (O2-.) by AM (p < 0.002). To gain insight into whether the activation of the AM was an inherent property of the cells or dependent on the in vivo milieu, AM were evaluated after 24 h in culture for O2-. release. In contrast to the findings in fresh AM, after 24 h in culture, O2-. release by HIV AM was not different from normals (p > 0.7), suggesting that these AM had been activated in vivo. To assess whether IFN-gamma could be mediating these effects, mRNA levels of the IP-10 gene (a gene specifically induced by increased concentrations of IFN-gamma) were quantified in AM. Strikingly, the IP-10 gene was expressed only in AM of HIV-seropositive individuals, suggesting the AM had been exposed to IFN-gamma in vivo. Overall, these observations are consistent with the concept that the HIV-seropositive state is associated with activation of AM, in part due to local exposure to IFN-gamma.

Adult↗
PubMed1998

Glucocorticoids protect against suppression of T cell responses in a murine model of acute ethanol exposure and thermal injury by regulating IL-6.

Previous reports by this laboratory demonstrated that acute alcohol exposure combined with a 15% body surface area dorsal scald injury results in significant reductions in delayed-type hypersensitivity (DTH) and splenocyte proliferative responses compared to either insult alone. Previous studies by this lab have also shown that these defects are mediated, in part, by increased production of interleukin-6 (IL-6). Because both alcohol exposure and thermal injury are known to modulate glucocorticoid (CORT) levels, and CORT regulates IL-6 gene expression, the relationship between circulating CORT and IL-6 production in burn + ethanol mice was examined. At 24 and 48 h post-burn, a positive correlation existed between circulating CORT levels and measurements of cellular immune function. Administration of exogenous CORT to burn + ethanol-treated mice resulted in significant restoration (to 60% of control) of DTH and splenocyte proliferative responses. This restoration was concomitant with a down-regulation of circulating and macrophage-derived IL-6. The specificity of CORT in modulating these responses was tested by assessing cellular immune function and IL-6 levels after glucocorticoid receptor blockade with RU486. Taken together, these data strongly suggest that under normal circumstances CORT protects burned mice from severe immune dysfunction, a protection that is not afforded to burn + ethanol-treated mice. Furthermore, the immune dysfunction observed in burn + ethanol mice may be due to a lack of glucocorticoid attenuation of IL-6.

Animals↗
PubMed2002

[Immunopathogenesis of severe wounds and traumas: possibilities of immune correction].

The authors describe the present-day views on the nature of immune dysfunctions in severe traumas. Based on personal clinical experiences and literature data the authors discuss the role of immune dysfunctions in pathogenesis of the traumatic disease. Special attention is given to the role of the immune system in the development of the life-threatening condition: polyorganic insufficiency whose formation mainly results from disorganization and functional failure of the system of immune reactivity. Clinical investigations have shown high effectiveness of early administration for severe wounds and traumas of a new means of immunocorrection--yeast recombinant interleukin-2 of man (preparation Roncoleukin). The administration of this immunocorrector in complex schemes of intensive therapy of the victims was shown to prevent the development of severe pyo-septic pathology and perfectly change the course of the traumatic disease.

Adult↗
PubMed1998

A twin and family study of the association between immune system dysfunction and dyslexia using blood serum immunoassay and survey data.

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.

Adolescent↗
PubMed1979

Environmental chemical-induced modification of cell-mediated immune responses.

It is therefore proposed that: 1) environmental chemicals can have specific mechanisms of toxicity and can influence antibody-mediated immunity while having no detectable effect on cell-mediated immunity, 2) immune dysfunction is related to exposure time to a chemical and the tissue concentration of that chemical, 3) recovery of immune function may occur even though chemical exposure continues, and 4) a single assay of immune function may not be appropriate to detect chemical induced immune dysfunction.

Animals↗
PubMed2001

IL-10 mediation of activation-induced TH1 cell apoptosis and lymphoid dysfunction in polymicrobial sepsis.

Recent studies suggest that increased activation-induced lymphocyte apoptosis (AICD) is detected in mouse splenocytes during polymicrobial sepsis which may contribute to lymphocyte immune dysfunction [i.e., decreased interleukin (IL-)2 and interferon-gamma (IFN-gamma) production] leading to the associated morbidity seen in those animals. Thus, we wanted to examine the hypothesis that immune suppressive agents, such as IL-4, IL-10 or prostaglandin E2(PGE2), known to be elevated in septic animals, also contribute to this increase in AICD. Here we demonstrate that the inclusion of monoclonal antibody (mAb) to IL-10, but not anti-IL-4 or ibuprofen (IBU), blunted this sepsis induced increase in splenocyte AICD. Additionally, septic mice deficient in the IL-10 gene product (-/-) showed neither an increase in AICD nor a loss of IL-2/IFN-gamma release capacity. Interestingly, mAb to IL-10 did not altered the extent of AICD in a Th2-cell line, but exogenous IL-10 did potentiate Th1-like cell line AICD. This was consistent with the finding that the increased AICD seen in septic mouse splenocytes was restricted largely to the CD4+ cells producing IL-2 (Th1-cells) and that mAb to IL-10 treatment suppressed this change. Furthermore, IL-10 appears to mediate its AICD effect by upregulation of the Fas receptor and Fas receptor signaling protein components, but not by altered expression of Bcl/Bax/Bad family members, in septic mouse splenocytes. To the extent that these processes contribute in a pathological fashion to the animal's capacity to survive sepsis we have previously observed that in vivo post-treatment of mice with mAb IL-10 markedly attenuated septic mortality. Collectively, these data indicate that in the septic mouse the Th2 cytokine IL-10 not only serves to actively induce Th1 lymphocyte immune dysfunction but also plays a role in their apoptotic depletion. These processes in turn appear to contribute to the animal's inability to ward off lethal septic challenge.

Animals↗
PubMed1998

Two novel mutations in exon 11 of the PAH gene (V1163del TG and P362T) associated with classic phenylketonuira and mild phenylketonuria. Mutations in brief no. 143. Online.

PKU is one of the commonest genetic disease in man, affecting 1/10,000 individuals. It presents a wide phenotypical spectrum, from classic PKU to moderate Hyperpheylalaninemia depending on the residual enzymatic activity. Two novel mutations 1163/1164delTG and P362T in exon 11 have been detected during the mutational screening of the PAH gene in 84 families. 1163/1164delTC can be confused with V388M if the mutational screening is performed with BsaAI restriction enzyme, this mutation in heterozigosis presents a moderate phenotype. P362T mutation in heterozigosis with V388M shows a classical PKU phenotype. We report here two new mutations in exon 11 of the PAH gene (GenBank U49897), V1163delTG and P362T (using cDNA sequence), detected during the analysis of 57 PKU and 36 HPA patients belonging to 84 unrelated families detected under a neonatal screening program performed in Catalonia.

DNA Mutational Analysis↗