interleukin-8 and Acquired-Immunodeficiency-Syndrome

Topics: Acquired Immunodeficiency Syndrome; Animals; Cell Movement; Chemokine CCL2; Chemokine CCL4; Chemokine CCL5; Chemokines; Dendritic Cells; Drug Design; Fibrosis; Humans; Inflammation; Interleukin-8; Lymphatic System; Macrophage Inflammatory Proteins; Pain; Receptors, Chemokine; Th1 Cells; Th2 Cells

Topics: Acquired Immunodeficiency Syndrome; Cytokines; Cytomegalovirus Retinitis; Humans; Interleukin-8; Tumor Necrosis Factor-alpha

The role of interleukins in the pathogenesis of lipodystrophy in HIV/AIDS-patients is still not understood. The aim of this study was to evaluate the relationship between serum levels of interleukins between HIV/AIDS-patients with or without lipodystrophy, as well as between different subgroups of lipodystrophy (lipoatrophy, lipohypertrophy, mixed-fat-redistribution) and patients without lipodystrophy.. Cross-sectional study of 66 HIV/AIDS patients, all Caucasians. Serum levels of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10) were measured using Cytokine-Array-1 on Evidence Investigator, Biochip Array Technology. The associations between interleukins and anthropometric and metabolic variables were estimated by Spearman-correlation. Analysis of covariance with bootstrapping method (ACBM) was used to examine relationship between interleukins and lipodystrophy categories adjusted for confounding variables.. The lipodystrophy was observed in 29 (44%) patients, while 15 (52%) had lipoatrophy, 4 (14%) lipohypertrophy and 10 (34%) patients had mixed fat redistribution. There were 37 (56%) patients without lipodystrophy. Significantly lower levels of IL-4 and IL-10 were observed in lipodystrophy vs. non-lipodystrophy (p=0.008; p=0.027, respectively). No differences were found relating IL-1α, IL-1β, IL-2, IL-6 and IL-8 levels in lipodystrophy vs. non-lipodystrophy. In patient subgroup with lipoatrophy, significantly lower levels of IL-4 and IL-10 were found when compared to non-lipodystrophy (p=0.043; p=0.031, respectively). In lipohypertrophy subgroup significantly lower levels of IL-4 were found when compared to non-lipodystrophy (p=0.003). In order to estimate the correlation of IL-4 and IL-10 and the presence of lipodystrophy, ACBM showed that correlation of IL-4 levels in patients with lipodystrophy remains statistically significant (p=0.004) in all types of lipodystrophy: lipoatrophy, lipohypertrophy and mix-fat-redistribution (p=0.027; p=0.009; p=0.017, respectively) after adjustment for age, BMI.. IL-4 and IL-10 levels were significantly lower in lipodystrophy vs. non-lipodystrophy. According to our knowledge, we showed for the first time significant correlation between IL-4 levels and lipodystrophy development in HIV/AIDS patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Body Mass Index; Cross-Sectional Studies; Female; Humans; Interleukin-10; Interleukin-1alpha; Interleukin-1beta; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Lipodystrophy; Male; Middle Aged

Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P = 0.008, R (2) = 0.258), HBDH (P = 0.001, R (2) = 0.335), and Ferritin (P = 0.005, R (2) = 0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P < 0.001; 1.11 ± 0.72, P = 0.043), larger AUC (95% CI 0.781-1.000, P < 0.001; 95% CI 0.592-0.917, P = 0.043), and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Biomarkers; Female; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Lactate Dehydrogenases; Male; Middle Aged; Pneumonia, Pneumocystis; Prognosis; ROC Curve; Severity of Illness Index; Tomography, X-Ray Computed

Interleukin-8 (IL-8) is the predominant cytokine expressed in the female genital tract of women with certain infectious/inflammatory conditions. IL-8 increased HIV-1 replication in T cells and to a greater extent in monocytes/macrophages in vitro. Physiological levels of IL-8 increased susceptibility to HIV-1 infection 5- to 8-fold in cervical explant tissues. Competitive inhibition of the IL-8 receptor CXCR2 with the small molecule inhibitor SB225002 resulted in a 45-70% decrease in cervical explant susceptibility to HIV-1 infection.

Topics: Acquired Immunodeficiency Syndrome; Cervix Uteri; Female; HIV-1; Humans; Interleukin-8; Phenylurea Compounds; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Virus Replication

In a case-control study, we studied the effect of a single nucleotide polymorphism in the IL-8 promoter on the risk of the development of AIDS-related Kaposi's sarcoma (KS). KS developed in 46% of individuals with the TT genotype and in 66% of AA/AT genotypes (P=0.038). Patients with TT genotype were rarely affected with visceral KS (7% versus 36%; P=0.06), which suggests that carriers of the TT genotype are protected from (severe) KS development.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Case-Control Studies; Genotype; Humans; Interleukin-8; Odds Ratio; Polymorphism, Genetic; Promoter Regions, Genetic; Risk Factors; Sarcoma, Kaposi

Regulation of cytokine and chemokine expression in microglia may have implications for CNS inflammatory disorders. In this study we examined the role of the cyclopentenone PG 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) in microglial inflammatory activation in primary cultures of human fetal microglia. 15d-PGJ(2) potently inhibited the expression of microglial cytokines (IL-1, TNF-alpha, and IL-6). We found that 15d-PGJ(2) had differential effects on the expression of two alpha-chemokines; whereas the Glu-Lys-Arg (ELR)(-) chemokine IFN-inducible protein-10/CXCL10 was inhibited, the ELR(+) chemokine IL-8/CXCL8 was not inhibited. These findings were shown in primary human microglia and the human monocytic cells line THP-1 cells, using diverse cell stimuli such as bacterial endotoxin, proinflammatory cytokines (IL-1 and TNF-alpha), IFN-beta, and HIV-1. Furthermore, IL-8/CXCL8 expression was induced by 15d-PGJ(2) alone or in combination with TNF-alpha or HIV-1. Combined results from EMSA, Western blot analysis, and immunocytochemistry showed that 15d-PGJ(2) inhibited NF-kappaB, Stat1, and p38 MAPK activation in microglia. Adenoviral transduction of super-repressor IkappaBalpha, dominant negative MKK6, and dominant negative Ras demonstrated that NF-kappaB and p38 MAPK were involved in LPS-induced IFN-inducible protein 10/CXCL10 production. Interestingly, although LPS-induced IL-8/CXCL8 was dependent on NF-kappaB, the baseline or 15d-PGJ(2)-mediated IL-8/CXCL8 production was NF-kappaB independent. Our results demonstrate that 15d-PGJ(2) has opposing effects on the expression of two alpha-chemokines. These data may have implications for CNS inflammatory diseases.

Topics: Acquired Immunodeficiency Syndrome; Chemokine CXCL10; Chemokines, CXC; DNA-Binding Proteins; Gene Expression Regulation; HIV-1; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-1; Interleukin-8; Microglia; Mitogen-Activated Protein Kinases; NF-kappa B; Prostaglandin D2; STAT1 Transcription Factor; Trans-Activators; Tumor Necrosis Factor-alpha

Human immunodeficiency virus type 1 (HIV-1) entry into CD4(+) cells requires the chemokine receptors CCR5 or CXCR4 as co-fusion receptors. We have previously demonstrated that chemokine receptors are capable of cross-regulating the functions of each other and, thus, affecting cellular responsiveness at the site of infection. To investigate the effects of chemokine receptor cross-regulation in HIV-1 infection, monocytes and MAGIC5 and rat basophilic leukemia (RBL-2H3) cell lines co-expressing the interleukin-8 (IL-8 or CXCL8) receptor CXCR1 and either CCR5 (ACCR5) or CXCR4 (ACXCR4) were generated. IL-8 activation of CXCR1, but not the IL-8 receptor CXCR2, cross-phosphorylated CCR5 and CXCR4 and cross-desensitized their responsiveness to RANTES (regulated on activation normal T cell expressed and secreted) (CCL5) and stromal derived factor (SDF-1 or CXCL12), respectively. CXCR1 activation internalized CCR5 but not CXCR4 despite cross-phosphorylation of both. IL-8 pretreatment also inhibited CCR5- but not CXCR4-mediated virus entry into MAGIC5 cells. A tail-deleted mutant of CXCR1, DeltaCXCR1, produced greater signals upon activation (Ca(2+) mobilization and phosphoinositide hydrolysis) and cross-internalized CXCR4, inhibiting HIV-1 entry. The protein kinase C inhibitor staurosporine prevented phosphorylation and internalization of the receptors by CXCR1 activation. Taken together, these results indicate that chemokine receptor-mediated HIV-1 cell infection is blocked by receptor internalization but not desensitization alone. Thus, activation of chemokine receptors unrelated to CCR5 and CXCR4 may play a cross-regulatory role in the infection and propagation of HIV-1. Since DeltaCXCR1, but not CXCR1, cross-internalized and cross-inhibited HIV-1 infection to CXCR4, the data indicate the importance of the signal strength of a receptor and, as a consequence, protein kinase C activation in the suppression of HIV-1 infection by cross-receptor-mediated internalization.

Topics: Acquired Immunodeficiency Syndrome; Calcium; HIV-1; Humans; Interleukin-8; Monocytes; Phosphorylation; Protein Kinase C; Receptors, CCR5; Receptors, CXCR4; Receptors, Interleukin-8A

Human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) is a side effect of highly active antiretroviral therapy of HIV-infected patients; however, the mechanism of the lipodystrophy and insulin resistance seen in this syndrome remains elusive. Adiponectin, an adipocyte-specific protein, is thought to play an important role in regulating insulin sensitivity. We investigated circulating levels and gene expression of adiponectin in subcutaneous abdominal adipose tissue (AT) from 18 HIV-infected patients with HALS compared with 18 HIV-infected patients without HALS. Implications of cytokines for adiponectin levels were investigated by determining circulating levels of TNF-alpha, IL-6, and IL-8 as well as gene expression of these cytokines in AT. HALS patients exhibited 40% reduced plasma adiponectin levels (P < 0.05) compared with non-HALS subjects. Correspondingly, adiponectin mRNA levels in AT were reduced by >50% (P = 0.06). HALS patients were insulin resistant, and a positive correlation was found between plasma adiponectin and insulin sensitivity (r = 0.55, P < 0.01) and percent limb fat (r = 0.61, P < 0.01). AT mRNA of TNF-alpha, IL-6, and IL-8 was increased in AT of HALS subjects (P < 0.05), and both AT TNF-alpha mRNA and plasma TNF-alpha were negatively correlated to plasma adiponectin (P < 0.05). Finally, TNF-alpha was found in vitro to inhibit human AT adiponectin mRNA by 80% (P < 0.05). In conclusion, HALS patients have reduced levels of plasma adiponectin and adiponectin mRNA in AT. Increased cytokine mRNA in AT is hypothesized to exert an inhibitory effect on adiponectin gene expression and, consequently, to play a role in the reduced plasma adiponectin levels found in HALS patients.

Topics: Acquired Immunodeficiency Syndrome; Adiponectin; Adipose Tissue; Adult; Antiretroviral Therapy, Highly Active; Body Composition; Body Mass Index; Cholesterol; Gene Expression; HIV-Associated Lipodystrophy Syndrome; Humans; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-6; Interleukin-8; Male; Middle Aged; Proteins; RNA, Messenger; Tumor Necrosis Factor-alpha

Production of the C-X-C chemokines interleukin-8 (IL-8) and growth-regulated oncogene alpha (GRO-alpha) in macrophages is stimulated by exposure to human immunodeficiency virus type 1 (HIV-1). We have demonstrated previously that GRO-alpha then stimulates HIV-1 replication in both T lymphocytes and macrophages. Here we demonstrate that IL-8 also stimulates HIV-1 replication in macrophages and T lymphocytes. We further show that increased levels of IL-8 are present in the lymphoid tissue of patients with AIDS. In addition, we demonstrate that compounds which inhibit the actions of IL-8 and GRO-alpha via their receptors, CXCR1 and CXCR2, also inhibit HIV-1 replication in both T lymphocytes and macrophages, indicating potential therapeutic uses for these compounds in HIV-1 infection and AIDS.

Topics: Acquired Immunodeficiency Syndrome; Antibodies; Chemokine CXCL1; Chemokines, CXC; Chemotactic Factors; Growth Substances; HIV-1; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Lymphoid Tissue; Macrophages; Monocytes; Phenylurea Compounds; Receptors, Interleukin-8A; Receptors, Interleukin-8B; T-Lymphocytes; Virus Replication

We examined the HIV-inhibitory effects previously found to be associated with scrub typhus infection. Individual 500 ml units of plasma from donors with mild scrub typhus were safety-tested, subjected to virucidal heat treatment, and administered to 10 HIV-1-infected recipients who were not receiving antiretroviral drugs. HIV-1 copy number fell three-fold or more in two recipients, and virus burden was reduced for 8 weeks in 70% (7/10) of recipients of a single plasma infusion, compared with the mean of three pre-infusion measurements. Scrub typhus donor plasma inhibited HIV-1 in vitro compared with normal human plasma and media controls. In the clearest in vivo response, reduction in viral load was accompanied by clinical improvement, a switchback from the syncytia-inducing to the non-syncytia-inducing phenotype, and decreases in CD8 cells and IL-6 levels. Scrub typhus infections can generate heat-stable, transferable plasma factors that exert prolonged anti-HIV effects. Whether variability in the results is due to different scrub typhus infections, different HIV infections or different individual responses, is unclear.

Topics: Acquired Immunodeficiency Syndrome; Adoptive Transfer; Adult; Blood Component Transfusion; DNA, Viral; Endothelin-1; Female; HIV-1; Humans; Immunoglobulin E; Interleukin-6; Interleukin-8; Lymphocyte Subsets; Male; Middle Aged; Orientia tsutsugamushi; Phenotype; Plasma; Proteinase Inhibitory Proteins, Secretory; Proteins; Scrub Typhus; Viral Load

Interleukin-8 (IL-8) production in vivo was monitored in four study groups: normal blood donors, patients with pulmonary tuberculosis (TB), patients with human immunodeficiency virus type 1 (HIV-1) infection, and dually infected (HIV/TB) patients. We show that whereas there was evidence of detectable levels of cell-associated IL-8 (mRNA and protein) in peripheral cells of healthy individuals, this was largely lost in the disease states studied. Coupled with this finding was significantly increased circulating levels of IL-8 in HIV-1-infected individuals with or without concomitant pulmonary TB (P < 0.001). On the other hand, the capacity of peripheral mononuclear cells to produce IL-8 spontaneously ex vivo was enhanced in HIV-1 and TB patients (P < 0.05) and many of the HIV/TB group, but their corresponding capacities to respond to various stimuli, in particular phytohemagglutinin, were significantly diminished compared to those of normal donors (P < 0.05). Circulating levels of IL-8 in a group of HIV/TB patients were significantly positively correlated with the percentage of polymorphonuclear leukocytes (PMN) in the peripheral circulation (r = 0.65; P = 0.01), the proportions of IL-8 receptor A (IL-8RA)-expressing (r = 0.86; P < 0.01) and IL-8RB-expressing (r = 0.77; P < 0.01) PMN, and the capacity of PMN to migrate in response to IL-8 as chemoattractant (r = 0.68; P < 0. 01). IL-8RB fluorescence intensity, however, was negatively correlated with plasma IL-8 levels (r = -0.73; P < 0.01). Our results suggest that altered regulation of IL-8 in HIV-1 may have important implications for antimicrobial defenses and for normal immune processes.

Topics: Acquired Immunodeficiency Syndrome; Adult; Female; HIV-1; Humans; Interleukin-8; Leukocytes, Mononuclear; Male; RNA, Messenger; Tuberculosis, Pulmonary

This study focused on the role of the HIV-derived viral protein, tat, in activating central nervous system (CNS)-derived endothelial cells (EC) to produce interleukin-8 (IL-8), a stimulator and chemoattractant for neutrophils and lymphocytes. Human CNS-EC treated with tat (100 ng/ml) demonstrated a 2 to 3 fold upregulation in IL-8 mRNA and protein. Tumor necrosis factor-alpha (TNF) and tat were found to act additively in upregulating IL-8 production. In contrast, transforming growth factor beta (TGF beta), appeared to down modulate tat-induced IL-8 production. These data suggest that extracellular tat, especially in the presence of TNF, may be responsible for the local production of IL-8.

Topics: Acquired Immunodeficiency Syndrome; Brain; Cell Movement; Cells, Cultured; Chemotaxis; Endothelium; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Regulation, Viral; Gene Products, tat; HIV-1; Humans; Interleukin-1; Interleukin-8; Male; Neutrophils; RNA, Messenger; tat Gene Products, Human Immunodeficiency Virus; Transforming Growth Factor beta

Mycobacterium avium is one of the most prevalent opportunistic infections in AIDS patients, and neither prophylaxis nor treatment against M. avium is effective. To evaluate host defense mechanisms against mycobacterial infections, studies investigated whether neutrophils from AIDS patients could inhibit the growth of M. avium in vitro and what cytokines enhance neutrophil function against M. avium. Peripheral blood neutrophils from human immunodeficiency virus-negative and AIDS patients were incubated with media, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-8, or macrophage-inhibitory proteins and infected with M. avium, and the inhibition of bacterial growth was determined. G-CSF (1000 U/mL) and GM-CSF (2000 U/mL) stimulated neutrophils from AIDS patients to significantly inhibit M. avium growth. These results demonstrate that neutrophils from AIDS patients can respond to exogenously supplied G-CSF or GM-CSF by inhibiting the growth of M. avium.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Blood Donors; Female; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-8; Lipopolysaccharides; Macrophages; Male; Middle Aged; Mycobacterium avium; Neutrophils; Recombinant Proteins

The role of cytokines was intensively discussed over the course of a two and a half day meeting sponsored by the US-JAPAN Cancer Cooperative Research Program of the Office of International Affairs, National Cancer Institute and held at The National Institutes of Health, Bethesda, Maryland on 15-17 January 1996. Most of the first day was devoted to a discussion of the role of cytokines in modulating angiogenesis and the consequent effect of this on tumor growth and metastases. This was followed by sessions on the effect of various cytokines in enhancing or suppressing immunological responses to tumors. Several presentations focused on the direct inhibitory or growth promoting effects of cytokines on tumor growth. The final session consisted of a comparison of the efficacy of different approaches to tumor vaccination including gene therapy, enhanced antigen presentation, use of polymeric carriers or of DNA vectors. For background information the reader is referred to appropriate chapters on the role of cytokines in neoplastic diseases (Oppenheim JJ, Rossio JL, Gearing AJH, eds. In Clinical Application of Cytokines: Role of Pathogenesis, Diagnosis and Therapy. Oxford University Press, New York, 1993 [1]).

Topics: Acquired Immunodeficiency Syndrome; Angiostatins; Animals; Chemokine CCL2; Colonic Neoplasms; Cytokines; Endothelial Growth Factors; Fibroblast Growth Factor 2; Gene Expression Regulation, Neoplastic; Genetic Therapy; Glycoproteins; Humans; Interleukin-10; Interleukin-12; Interleukin-2; Interleukin-8; Keratinocytes; Lymphokines; Neoplasms; Neovascularization, Pathologic; Peptide Fragments; Plasminogen; Recombinant Proteins; Sarcoma, Kaposi; Th1 Cells; Th2 Cells; Tissue Inhibitor of Metalloproteinases; Tumor Necrosis Factor-alpha; Ultraviolet Rays; Vaccines; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Impaired polymorphonuclear neutrophil (PMN) function may contribute to the onset of certain life-threatening bacterial and fungal infections in human immunodeficiency virus (HIV)-infected patients. Published data on PMN functional activity in HIV infection are controversial, possibly because most studies have involved PMNs isolated from their blood environment by means of various procedures that may differently affect surface receptor expression and thereby alter cellular responses. We therefore used flow cytometry to study the expression of adhesion molecules at the PMN surface, actin polymerization, and the oxidative burst of whole-blood polymorphonuclear neutrophils in 42 HIV-infected patients at different stages of the disease. These PMNs were activated in vivo, as demonstrated by increased expression of the adhesion molecule CD11b/CD18, reduced L-selectin antigen expression, increased actin polymerization, and increased H2O2 production. The alterations were present in asymptomatic patients with CD4+ cell counts greater than 500/microL and did not increase with the progression of the disease. Stimulation by bacterial N-formyl peptides showed dysregulation of L-selectin shedding and decreased H2O2 production after ex vivo priming with tumor necrosis factor alpha or interleukin-8 (IL-8). These latter impairments, which correlated with the decrease in CD4+ lymphocyte numbers and with IL-8 and IL-6 plasma levels, could contribute to the increased susceptibility of HIV-infected patients to bacterial infections.

Topics: Acquired Immunodeficiency Syndrome; Actins; Adult; CD4 Lymphocyte Count; Cell Adhesion Molecules; Female; Humans; Hydrogen Peroxide; Interleukin-6; Interleukin-8; L-Selectin; Leukocyte Count; Lymphocyte Count; Macrophage-1 Antigen; Male; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine; Neutrophil Activation; Neutrophils; Respiratory Burst; Tumor Necrosis Factor-alpha

We examined the in vitro release of interleukin 8 (IL-8), interleukin 10 (IL-10), and interleukin 12 (IL-12) by alveolar macrophages from normal volunteers and HIV-1-infected subjects. Normal volunteers had very low levels of IL-8 and IL-10 and undetectable IL-12 in the cell-free bronchoalveolar lavage fluid (BALF). Asymptomatic HIV-1-infected subjects had elevated levels of IL-8 and IL-10 in their BALF, and HIV-1-infected subjects with nonspecific interstitial pneumonitis (NIP) or infected with Pneumocystis carinii had the highest BALF levels of IL-10 and IL-8. It was found that alveolar macrophages from asymptomatic HIV-1 subjects and from NIP subjects spontaneously released elevated IL-8, IL-10, and IL-12. However, AIDS subjects infected with P. carinii had cells that released elevated levels of IL-10 and IL-8, but low levels of IL-12. When alveolar macrophages were stimulated with Staphylococcus aureus Cowan (SAC), cells from normal volunteers responded with a considerably increased release of IL-8, IL-10, and IL-12; cells from HIV-1-infected subjects without P. carinii infection responded with a moderate increase in release of all three monokines. SAC stimulation did not enhance the release of monokines by cells from AIDS subjects with P. carinii infection, and IL-12 levels remained low. There was no strict relationship between spontaneous cytokine release and p24 HIV-1 antigen expression by alveolar macrophages. Finally, we showed that neutralizing IL-10 production by alveolar macrophages from AIDS subjects substantially increased IL-12 releasability.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Bronchoalveolar Lavage Fluid; Genes, gag; HIV Core Protein p24; HIV-1; Humans; Interleukin-10; Interleukin-12; Interleukin-8; Lipopolysaccharides; Lung Diseases, Interstitial; Macrophages, Alveolar; Staphylococcus aureus

The effects of human interferon-alpha (IFN-alpha) on the release of an antimicrobial interleukin, interleukin-8 (IL-8), from human immunodeficiency virus type 1 (HIV-1)-infected myelomonocytic cell line, U937, were studied in vitro to evaluate the potential of IFN-alpha in the management of acquired immunodeficiency syndrome (AIDS)-associated opportunistic diseases. The latently HIV-1-infected U937 cells (U937/HIV-1(L)) showed a marked reduction of IL-8 secretion as compared to uninfected U937 cells, whereas IL-8 release from productively HIV-1-infected U937 cells was comparable to uninfected cells. The IFN-alpha recovered partially the reduced IL-8 level from U937/HIV-1(L) cells in a dose-dependent manner. Any significant inhibition of IFN-alpha-augmented IL-8 secrement by anti-IL-1 antibody was not observed, suggesting that the enhanced IL-8 secretion occurred without augmenting IL-1 production. The IFN-alpha-augmented IL-8 secretion from latently HIV-1-infected U937 cells may suggest a beneficial potential of IFN-alpha in a treatment of bacterial or fungal infection frequently seen in patients with progressive stages of HIV-1 infection.

Topics: Acquired Immunodeficiency Syndrome; Evaluation Studies as Topic; Humans; Interferon-alpha; Interleukin-8; Monocytes; Tumor Cells, Cultured; Virus Latency

Activation of the cellular transcription factor nuclear factor-kappa B (NF-kappa B) by cytokines and other immunostimulants has been tightly linked with enhanced replication of human immunodeficiency virus-type 1 (HIV-1) in infected cells. Various immunomodulators are currently being examined in animal and human trials for their suitability as adjuvants in potential vaccines against acquired immunodeficiency syndrome (AIDS). It may prove to be beneficial to select adjuvants that do not induce NF-kappa B activation and particularly if the vaccines are to be aimed at seropositive individuals. We have examined a battery of synthetic immunostimulants of the muramyl peptide family for their ability to activate NF-kappa B in human and mouse cell lines. In this report, we demonstrate selective activation of NF-kappa B in different cell lines and by different muramyl peptides possessing immunostimulatory activities. The mechanism of such activation is apparently via production of reactive oxygen intermediates (ROI) since pretreatment of cells with antioxidants blocked subsequent activation of NF-kappa B. However, among all the molecules tested only one lipophilic, non-pyrogenic adjuvant active muramyl peptide showed a complete lack of NF-kappa B activation in all cell lines tested. This molecule could well become the adjuvant of choice in future AIDS vaccines.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Animals; Antioxidants; Base Sequence; Cell Line; Gene Expression; Humans; In Vitro Techniques; Interleukin-8; Mice; Molecular Sequence Data; NF-kappa B; Oligodeoxyribonucleotides; Reactive Oxygen Species; Structure-Activity Relationship