interleukin-8 and Measles

After measles vaccine (MV), all-cause mortality is reduced more than can be explained by the prevention of measles, especially in females.. We aimed to study the biological mechanisms underlying the observed non-specific and sex-differential effects of MV on mortality.. Within a large randomised trial of MV at 4.5 months of age blood samples were obtained before and six weeks after randomisation to early MV or no early MV. We measured concentrations of cytokines and soluble receptors from plasma (interleukin-1 receptor agonist (IL-1Ra), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, soluble urokinase-type plasminogen activator receptor), and secreted cytokines (interferon-γ, TNF-α, IL-5, IL-10, IL-13, IL-17) after in vitro challenge with innate agonists and recall antigens. We analysed the effect of MV in multiple imputation regression, overall and stratified by sex. The majority of the infants had previously been enrolled in a randomised trial of neonatal vitamin A. Post hoc we explored the potential effect modification by neonatal vitamin A.. Overall, MV versus no MV was associated with higher plasma MCP-1 levels, but the effect was only significant among females. Additionally, MV was associated with increased plasma IL-1Ra. MV had significantly positive effects on plasma IL-1Ra and IL-8 levels in females, but not in males. These effects were strongest in vitamin A supplemented infants. Vitamin A shifted the effect of MV in a pro-inflammatory direction.. In this explorative study we found indications of sex-differential effects of MV on several of the plasma biomarkers investigated; in particular MV increased levels in females, most strongly in vitamin A recipients. The findings support that sex and micronutrient supplementation should be taken into account when analysing vaccine effects.. clinicaltrials.gov number NCT 00168545.

Topics: Chemokine CCL2; Cytokines; Female; Guinea-Bissau; Humans; Infant; Interleukin 1 Receptor Antagonist Protein; Interleukin-8; Male; Measles; Measles Vaccine; Regression Analysis; Sex Factors; Vitamin A

Helicobacter pylori is a Gram-negative, spiral-shaped microorganism associated with acute and chronic gastritis, peptic ulcer, gastric cancer and gastric lymphomas in humans. H. pylori neutrophil-activating protein (NAP) is a major virulence factor playing a central role in pathogenesis of mucosal inflammation by immune cell attraction and Th1 cytokine response polarization. NAP is protective antigen and promising vaccine candidate against H. pylori infection. Here we present the development of measles virus (MV) vaccine strain encoding the NAP antigen. In order to facilitate the extracellular transport and detection, NAP was inserted in the human lambda immunoglobulin chain replacing a major part of the variable domain. We generated two MV vectors expressing secretory NAP forms: MV-lambda-NAP encoding the full-length constant lambda light chain domain and MV-s-NAP encoding only the N-terminus of the lambda light chain with the leader peptide. Immunization of MV permissive Ifnarko-CD46Ge transgenic mice by a single intraperitoneal injection of the NAP-expressing strains induced a robust, long-term humoral and cellular immune response against MV. Nine months post vaccination measles-neutralizing antibody titers were above the serum level considered protective for humans. Furthermore, all animals immunized with MV strains expressing the secretory NAP antigen developed strong humoral immunity against NAP, reaching titers >1:10,000 within 2-4 weeks. IFN-γ ELISpot assay confirmed that NAP-encoding MV vectors can also stimulate NAP-specific cell-mediated immunity. Our data demonstrate that MV is an excellent vector platform for expression of bacterial antigens and development of vaccines for H. pylori immunoprophylaxis in humans.

Topics: Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Antigens, Bacterial; Bacterial Proteins; Bacterial Vaccines; Cell Line, Tumor; Chlorocebus aethiops; Female; Helicobacter Infections; Helicobacter pylori; Humans; Immunity, Humoral; Interferon-gamma; Interleukin-8; Measles; Measles virus; Mice; Mice, Knockout; Mice, Transgenic; Neutralization Tests; Recombinant Proteins; Vaccines, Attenuated; Vero Cells

Measles virus infection may progress to a chronic obstructive process including bronchiolitis obliterans (BO). This study investigates pulmonary cellular profiles and interleukin (IL)-8 levels in patients with BO following the measles.. BAL fluid was obtained from 12 children with BO who had a history of measles pneumonia during an outbreak in 2000 and 2001. BAL cell counts and differentials were compared to control patients as well as BAL IL-8 levels, which were measured by enzyme-linked immunosorbent assay. Immunohistochemical staining of BAL cells and three open-lung biopsy specimens were also analyzed for T-cell surface markers CD3, CD4, and CD8.. BAL cellular profiles were characterized by a significantly increased percentage of neutrophils in the measles BO group (median, 16.0%) compared to the control group (2.3%) [p < 0.01]. BAL IL-8 levels were also markedly increased in the measles BO group (mean +/- SD, 418.6 +/- 286.0 pg/mL) compared to the control group (92.8 +/- 126.7 pg/mL) [p < 0.01]. BAL IL-8 levels correlated significantly with neutrophil percentages in both the measles BO group (r = 0.86, p = 0.000) and the control group (r = 0.79, p = 0.007). The lymphocyte subsets were characterized by a significantly increased number of CD8+ cells, resulting in a decreased CD4/CD8 ratio in the BAL and the biopsy specimens.. These results suggest that pulmonary neutrophils and IL-8, along with CD8+ T lymphocytes may play an important role in the pathogenesis of BO after measles virus infection.

Topics: Biopsy; Bronchiolitis Obliterans; Bronchoalveolar Lavage Fluid; Bronchoscopy; Case-Control Studies; CD3 Complex; CD8 Antigens; Cell Count; Child, Preschool; Female; Humans; Infant; Interleukin-8; Lung; Male; Measles; Neutrophils; T-Lymphocytes; Tomography, X-Ray Computed

Measles virus (MV) infection primarily targets epithelial cells of the respiratory tract, which have the potential to synthesize a variety of cytokines. In this report, we studied the effect of MV infection on the production of interleukin (IL)-8 by the pulmonary epithelial cells. A549 cells, a lower airway epithelial cell line, produced IL-8 after MV inoculation in a dose- and time-dependent manner. The IL-8 production was little affected by UV-inactivation of MV and scarcely suppressed by cycloheximide treatment. These results indicated that MV particle binding to and/or incorporation into cells stimulated IL-8 expression in A549 cells.

Topics: Animals; Cell Line, Tumor; Cycloheximide; Epithelial Cells; Interleukin-8; Lung; Measles; Measles virus; Polymerase Chain Reaction; Protein Synthesis Inhibitors; RNA, Messenger; Virus Replication

We hypothesized that acute measles infection imposes severe metabolic demands on malnourished children. Nigerian rural communities, characterized by severe poverty and extensive malnutrition, served as site for this study. Sixty-five children (mean [+/-SD] age 2.67 +/- 1.96 years) with measles and a randomly selected equal number of children (age 2.83 +/- 1.23 years) from the same communities but measles-free were studied. Both groups were serologically negative for human immunodeficiency virus. The percentages of nonmeasles group who were underweight and wasted as exemplified by weight for age (WAZ) and weight for height (WHZ) scores less than -2.0 SD were 43% and 23%, respectively. Comparative values for the measles group (66% and 54% respectively) were significantly (P < 0.01 or 0.001) different. Compared to the controls, measles-infected children had significantly (P < 0.001) higher plasma cortisol level, marked hyporetinemia (plasma retinol 0.62 +/- 0.24 micromol/L) and prominent reduction (P < 0.002) in the sum of serum essential amino acids. Measles promoted a TH(1) to TH(2) cytokine shift, with severe depletion of plasma interleukin (IL)-12, a key cytokine in the development of cell mediated immunity. IL-6, a key stimulator of hepatic acute phase protein response, was prominently (P < 0.002) increased in plasma in measles-infected children. Glucocorticoids exert effects on cytokine expression, as well as on cytokine receptor expression and cytokine-regulated biological responses. They enhance synergistically, the effects of IL-1 and IL-6 type cytokines on many acute phase proteins. Because of the prominent increase in circulating level of cortisol in acute measles, glucocorticoid treatment for associated sepsis may pose serious problems. Additionally, glucocorticoids antagonize several effects of retinoids at cellular and transcriptional levels, thus suggesting that hypercortisolemia may increase the requirement for retinoids.

Topics: Amino Acids, Essential; Anthropometry; Child, Preschool; Cytokines; Humans; Hydrocortisone; Infant; Interleukin-1; Interleukin-12; Interleukin-6; Interleukin-8; Malnutrition; Measles; Nigeria; Th1 Cells; Th2 Cells; Vitamin A