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Biomedical subjects

Y Mouton

Publications and source records attributed to Y Mouton.

At least 55 records · Page 3Linked to original sources
PubMed1999

Biological properties of interferon-alpha produced Ex vivo by whole blood of patients infected by human immunodeficiency virus-1.

We investigated the biological properties of interferon (IFN)-alpha produced by Sendai virus (SV)-activated whole blood cultures in 20 patients infected with human immunodeficiency virus (HIV)-1 and 24 healthy controls. Supernatants of cultures were assayed for IFN-alpha by using an immunological method (DELFIA), biological methods and an in-vitro MxA induction assay. The levels of intracellular MxA protein were detected by an immunochemiluminescence assay. The levels of IFN-alpha in patients measured by DELFIA were significantly lower than those in healthy controls (P < 0.0001), but the antiviral activity of IFN-alpha in patients infected with HIV-1 was lower than predicted from DELFIA. The IFN-alpha produced by cells of patients infected with HIV-1 was able to induce MxA protein in human amnions WISH cells but was unable to protect these cells against Vesicular Stomatitis Virus (VSV)-induced cytopathic effects. A relative increased capability to induce the production of MxA protein in vitro was observed with the IFN-alpha contained in culture supernatant of virus-activated whole blood of HIV-1-infected patients with increased levels of MxA in their peripheral blood. These data suggest that biological properties of IFN-alpha produced in the course of HIV-1 infection are different from those observed with IFN-alpha of healthy subjects.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Specific immune response to human immunodeficiency virus (HIV)-1 in patients assessed through the production of interferon-gamma and interleukin-4 in HIV-1 p24-activated whole blood cultures: relationship with the viral load in plasma.

We studied the in vitro HIV-1 antigen-stimulated production of IFN-gamma and IL-4 in HIV-1-infected patients and its relationship with viral replication as assessed through the plasma level of HIV-1 RNA. The levels of IFN-gamma and IL-4 were higher in supernatants of stimulated whole blood cultures than in stimulated peripheral blood mononuclear cell cultures, therefore whole blood cultures were used in the rest of the study. Specific IFN-gamma and IL-4 responses to HIV-1 p24 antigen were observed in HIV-1-infected patients but not in healthy controls (n = 23). A lower proportion of individuals with a positive IFN-gamma response to HIV-1 p24 was observed in patients at a declining clinical stage: 62% in asymptomatic patients (CDC group A, n = 16) versus 19% in symptomatic patients (CDC groups B and C, n = 21; P = 0.007, chi2 testing), whereas the proportion of individuals with a positive IL-4 response to HIV-1 p24 was almost similar in both groups of patients (25% versus 23.8%). Increased IL-4 production by HIV-1 p24-activated immunocompetent cells of patients and a predominant IL-4 response to HIV-1 p24 (with IL-4/IFN-gamma > 1) were positively correlated with an increased viral load. In contrast, there was no correlation between the mitogen-stimulated production of IL-4 and IFN-gamma and the viral load in plasma. The CD8 T cells from whole blood of patients, but not from controls played a significant role in the HIV-1 p24-activated production of IFN-gamma and IL-4. In conclusion, HIV-1-antigen-stimulated whole blood appears to be a valuable tool to study the production of IL-4 in HIV-1-infected patients. The cytokine profile pattern in response to epitopes of HIV-1 gag p24 may play an important role in the host immune response to HIV-1.

Adult↗
PubMed1999

Interleukin-16 (IL-16) inhibits human immunodeficiency virus replication in cells from infected subjects, and serum IL-16 levels drop with disease progression.

The role of recombinant interleukin-16 (rIL-16) in regulating human immunodeficiency virus type 1 (HIV-1) replication in endogenously infected cells has been investigated. Cultures of CD8 cell-depleted mitogen-activated lymphocytes from 22 of 26 HIV-1-infected subjects presented variable levels of secreted p24 antigen. The presence of rIL-16 throughout the 14-day culture period dramatically inhibited p24 release into the culture supernatants. This effect was found to be mediated through inhibition of viral transcription but to be independent of the induced levels of other cytokines or chemokines known to regulate viral replication. Analysis of serum samples from HIV-1-infected subjects over a period of 8 years showed maintained or even increased IL-16 levels during the whole asymptomatic phase and a significant drop on progression to disease. These results strongly support a potential therapeutic value of rIL-16 in HIV-1 infection and the use of serum IL-16 levels to monitor disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1998

A decreased production of IL12 in vitro is associated with isolation of cytopathic HIV-1 strains in HIV-1-infected patients.

The changes in type 1 (IL12, IFN gamma, IL2) and type 2(IL4, IL10) cytokine profiles may be associated with virological parameters of progression of the disease in HIV-1-infected patients. The production of cytokines was studied in LPS + PHA-activated whole-blood culture in HIV-1-infected individuals at different stages of the disease. The association was investigated between IL12p40 and IL12p70 profiles and other cytokines (IFN gamma, IL4, IL10), as well as the isolation of cytopathogenic HIV-1 strains. The phenotype of HIV strains was studied by a micromethod based on P4 cell line, allowing detection of cytopathic effects of HIV-1 isolates (syncytium-induction and cell-killing without syncytium induction). The individual variations in IL12p40 and IL12p70 production were limited in the healthy controls. Low values were observed in HIV-1-infected patients. The production of IL12 (p40 and p70) and the IL12p70/IL4 ratio and the IFN gamma/IL4 ratio were significantly lower in patients with cytopathic isolates compared with patients with noncytopathic isolates, and a correlation was obtained between the values of IL12 (IL12p40 and IL12p70) and those of IFN gamma/IL4 ratio. There was no increase in the secretion of IL4 and IL10 in patients with cytopathic strains compared with other patients. The results indicate a decreased production of type 1 cytokines (IL12, IFN gamma) in the presence of a relatively preserved production of type 2 cytokines (IL4, IL10) in HIV-1-infected patients. In conclusion, the defect of production of IL12 by whole blood is associated with virological correlates of progression of HIV-1 disease.

Cell Line↗
PubMed1998

Recombinant human IL-16 inhibits HIV-1 replication and protects against activation-induced cell death (AICD).

The chemoattractant cytokine IL- 16 has been reported to suppress lymphocyte activation and to inhibit HIV-1 replication in acutely infected T cells. We have cloned and expressed human IL-16 in Escherichia coli and investigated whether the recombinant protein could regulate the level of lymphocyte apoptosis from HIV-1-infected subjects. After purification and refolding, only 2-10% of the recombinant cytokine was present in a biologically active homotetrameric form. This could explain the need for high concentrations of the bacterially derived IL- 16 to induce significant inhibition of HIV-1 replication. Addition of IL-16 to unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-1-infected subjects did not modify the observed level of spontaneous lymphocyte apoptosis. In contrast, IL-16 added to PBMC cultures stimulated with anti-CD3, anti-CD95 or dexamethasone reduced significantly the percentage of lymphocytes undergoing AICD. This effect was found to correlate with the ability of the cytokine to decrease CD95 expression on activated CD4+ T cells. Comparative studies on PBMC from healthy individuals indicated that the regulation of apoptosis levels by IL-16 is a complex phenomenon and could depend on the nature of the activator used and/or the immune status of lymphocytes tested. The outcome of CD4 cross-linking on T cells by various ligands is discussed in the context of the observed beneficial activities of IL- 16 and its potential role in the treatment of HIV disease.

Apoptosis↗
PubMed1998

RANTES production in HIV-1 antigen-stimulated whole blood culture: relationship with type 1 immune response and plasma viral load in individuals infected with HIV-1.

Host factors which control replication and clearance of human immunodeficiency virus (HIV) are poorly understood. RANTES (regulated on activation, normal T cell expressed and secreted) and other beta-chemokines may be HIV-1-suppressive factors but their role in the progression of HIV-1 infection is a subject of controversy. We investigated the relationship between production of RANTES and correlates of disease progression in 15 patients infected with HIV-1. We used whole blood culture to study the production of RANTES, interferon (IFN)-gamma, interleukin (IL)-4 and IL-13 in response to supernatant of T cells infected with HIV-1. A defect of RANTES production was associated with a predominant type 2 and decreased type 1 cytokine profile (IL-4 and/or IL- 13 > IFN-gamma). We obtained a positive correlation between RANTES and IFN-gamma (P = 0.004) and the ratio of type 1 and type 2 cytokines IFN-gamma/IL-4 (P = 0.04) and IFN-gamma/IL-13 (P = 0.003), and a negative correlation between RANTES production and HIV-1 RNA copy number in plasma (P = 0.01). The same pattern of correlation was observed between HIV-1 p24-stimulated production of RANTES and the plasma viral load (P = 0.02, n = 15). The measurement of RANTES produced by heparinized whole blood in response to HIV-1 antigens appears as a potentially valuable tool to assess the defect of type 1 immune response in individuals infected with HIV-1 and to define whether the absence of a RANTES response may play a role in the increased rate of HIV-1 replication.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Production of interleukin-4, interferon (IFN)-gamma and IFN-alpha in human immunodeficiency virus-1 infection: an imbalance of type 1 and type 2 cytokines may reduce the synthesis of IFN-alpha.

Interferon-alpha (IFN-alpha) is an important molecule in the antiviral response, but cells from HIV-1-infected individuals show a reduced ability to secrete IFN-alpha. We investigated an association between an imbalance of type 1/type2 cytokines and the production of IFN-alpha in HIV-1 infection. We used whole blood culture to study the cytokine production profile, interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), in response to HIV-1 antigens and to study the Sendai Virus and HSV-1-induced-production of IFN-alpha in seven HIV-1-infected patients. An impaired synthesis of IFN-alpha was obtained in patients with a predominant IL-4 production (IL-4 > IFN-gamma), and we found a positive correlation between the ex vivo production of IFN-alpha and the IFN-gamma/IL-4 ratio but not with the HIV RNA copy number in plasma. We investigated the role of T-cell-derived cytokines in the in vitro production of IFN-alpha by PBMC from eight healthy donors, activated with Sendai Virus or HSV-1. Whereas type 2 cytokines (IL-4, IL-13) inhibited virus-induced IFN-alpha synthesis, on the contrary, type 1 cytokines (IL-2, IFN-gamma) enhanced it. A disarray in the T-cell-derived cytokine response may play a role in the defect of IFN-alpha production in HIV-1-infected individuals. Further investigations are needed to explore this hypothesis.

Adult↗
PubMed1998

Tolerance, compliance and psychological consequences of post-exposure prophylaxis in health-care workers.

Our objectives were to evaluate tolerance and compliance of post-exposure triple therapy in health-care workers (HCWs) by retrospective observational study. Structured telephone interview of HCWs identified through data from antiretroviral prescribing centres. Twenty HCWs who received triple prophylaxis were identified over one year. Sixteen agreed to participate in the study. All but one source patient had documented HIV infection. Half HCWs were not aware of post-exposure therapy. Most HCWs received a zidovudine, lamivudine and indinavir combination. All completed at least 4 weeks of therapy. Only 50% received their first dosage less than 4 h after exposure. Nearly all experienced adverse events, mostly digestive (nausea and abdominal pain n=15) or psychological (anxiety and depression n=15), none resulting in therapy discontinuation. Most events occurred 2 to 7 days after therapy initiation. Most modified their sexual life with abstinence or condom use. Compliance was excellent. Half HCWs did not miss any tablet, 4 forgot one dosing a month and 4 one dosing a week. Follow up is over 6 months in all but one HCW. No HIV seroconversion has been observed to date. In France, post-exposure triple antiretroviral therapy is widely available 24 h a day in every emergency room but further training and development of HCWs is needed to decrease consulting time and increase referral to specialized physicians. Notable moderate adverse events, both physical and psychological are noted, however, compliance is excellent.

Adult↗
PubMed1997

Procalcitonin as a marker of bacterial sepsis in patients infected with HIV-1.

Procalcitonin (ProCT) is a recently described marker of severe sepsis. It was decided to assess the value of proCT as a marker of secondary infection in patients infected with HIV-1. ProCT plasma levels were measured by immunoluminometric assay in a prospective study in 155 HIV-infected individuals: 102 asymptomatic and 53 with lever or suspected secondary infections. The baseline plasma level of ProCT was low (0.5 ng/ml +/- 0.37), even in the latest stages of the disease, and did not differ from the values of healthy subjects (0.54 ng/ml +/- 0.08). EDTA-treated whole blood was collected from patients before starting specific antimicrobial therapy. No elevation of ProCT level was detected in HIV-infected patients with evolving secondary infections including PCP (n = 4), cerebral toxoplasmosis (n = 4), viral infections (n = 9), mycobacterial infections (n = 5), localized bacterial (n = 12) and fungal infections (n = 4), malignancies (n = 3), and in various associated infectious and non-infectious febrile events (n = 13). All these plasma values were lower than 2.1 ng/ml. In contrast, high ProCT plasma levels were detected in one HIV-infected patient with a septicaemic Haemophilus influenzae infection (16.5 ng/ml) and another one with a septicaemic Pseudomonas aeruginosa infection (44.1 ng/ ml), ProCT values decreased rapidly under appropriate therapy. ProCT seems to be a specific marker of bacterial sepsis in HIV-infected patients, as no increase in other secondary infections could be detected in those patients. A rapid determination of ProCT level could be useful to confirm or refute bacterial sepsis for a better management of febrile HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

Failure of intravenous antibiotic therapy of multiple temporal brain abscesses due to Propionibacterium acnes requiring temporal lobectomy.

Propionibacterium acnes is a common skin colonizer. Its involvement in brain abscesses is generally described as a complication of neurosurgical intervention. Propionibacterium acnes is susceptible to antibiotics used as treatment of anaerobic infections, except for the 5-nitroimidazoles. Surgical excision or drainage of a simple abscess combined with a long course of antibiotics is considered the treatment of choice. A case of a patient with multiple brain abscesses located in the right temporal lobe that occurred after the manipulation of an abscess of the right upper maxillary is reported. The patient did not improve despite a prolonged course of high-dose intravenous penicillin plus thiamphenicol and cure was finally obtained after the excision of the right temporal lobe. Culture of the purulent material and the shell of the abscesses yielded P. acnes which was sensitive to all the antibiotics administered to the patient up to the intervention. The temporal lobectomy was followed by a 6-month course of ofloxacin. One year after the intervention, the patient remained apyretic without any other abscess on cranial computed tomography scan.

Adult↗
PubMed1997

Role of nitric oxide in the regulation of lymphocyte apoptosis and HIV-1 replication.

Nitric oxide (NO) has been implicated in certain immunopathogenetic mechanisms during the course of infection with human immunodeficiency virus (HIV). We have evaluated the levels of NO release and lymphocyte apoptosis in peripheral blood mononuclear cell (PBMC) cultures from HIV-1 infected subjects and healthy controls. We have also examined these 2 parameters in parallel cultures maintained under conditions where either NO synthesis was inhibited or high level of NO was present. Nitrite contents in culture supernatants were measured as the stable end products of the released NO. Levels of spontaneous apoptosis and activation-induced cell death (AICD) by anti-CD3 or by phytohemagglutinin were evaluated using flow cytometry. Additional experiments were also aimed at addressing a potential link between NO synthesis and HIV-1 replication in human monocyte-derived macrophages (MDMs). Acutely infected MDMs with HIV-1Bal were maintained in culture, without any additional activation signal, for a period of 14 days. Nitrites in the supernatants and mRNA accumulation of the inducible NO synthase (iNOS) in infected cells were assessed over the whole culture period. In addition, the effect of blocking NO synthesis during and after infection of MDMs, using an inhibitor of NO, was evaluated on the level of viral replication as measured by the presence of P24 antigen in the supernatants. Similarly, the effect on HIV replication of high NO levels in MDM cultures, supplied by a donor of NO during the 24 h period of infection, was also studied. We conclude that no elevation in NO release could be detected in PBMC cultures from HIV-1 infected subjects and that modulation of NO content may slightly regulate the level of spontaneous lymphocyte apoptosis but not that of AICD. Infection of MDMs with HIV-1 does not seem to induce detectable NO release or iNOS mRNA accumulation. Similarly, neither inhibition of NO synthesis nor the presence of high NO levels during the infection period could modify the outcome of virus replication in macrophages.

Apoptosis↗
PubMed1997

Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. Fédération National des Centres de Lutte contre le SIDA.

OBJECTIVE: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. DESIGN: Multicentric, observational, retrospective cohort study. SETTING: Ten AIDS reference centres in France. PATIENTS: All patients followed in each centre from September 1995 through October 1996. MAIN OUTCOME MEASURES: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. RESULTS: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month). CONCLUSIONS: This study supports the extensive use of HAART in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗