Cytokine profiles using whole-blood assays can discriminate between tuberculosis patients and healthy endemic controls in a BCG-vaccinated population


Hussain, R; Kaleem, A; Shahid, F; Dojki, M; Jamil, B; Mehmood, H; Dawood, G; Dockrell, HM; (2002) Cytokine profiles using whole-blood assays can discriminate between tuberculosis patients and healthy endemic controls in a BCG-vaccinated population. Journal of immunological methods, 264 (1-2). pp. 95-108. ISSN 0022-1759 DOI: 10.1016/S0022-1759(02)00092-3

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Abstract

Whole-blood assays (WB) provide a simple tool for assessing immune cytokine profiles which may be useful laboratory predictors of early disease, aiding the evaluation of new tuberculosis (TB) vaccines and offering insights into disease pathogenesis. Although BCG does not provide protection against pulmonary disease in TB endemic areas, it does modulate immune responses to mycobacterial antigens. It is important, therefore, to evaluate any new tool in an endemic setting in both BCG vaccinees and patients with tuberculosis. We have assessed the optimal conditions in terms of dose and kinetics of those cytokines which are released early (TNF-alpha, IL6 and TGF-beta, IL10) or (interferon [IFN]-gamma and IL5) in WB cultures stimulated with mitogens and mycobacterial antigens. Responses were studied in parallel in untreated TB patients and endemic control groups. Optimal responses to LPS (predominantly monocyte-derived) occurred on days 1-2, whereas for PHA (predominantly T-cell-derived), they were on days 3-5. Secreted Mycobacterium tuberculosis culture filtrate proteins (CFP) provided a stronger stimulus for monocyte-derived cytokines compared to PPD, but both antigens were comparable for induction of T-cell cytokines. Using unpaired Student's t-tests, pulmonary tuberculosis patients (P.TB; n=11), in response to CFP, showed higher monocyte-derived IL6 (p=0.023) and IL10 (p=0.042) compared to endemic controls (EC; n=13), and significantly suppressed T-cell-derived IFN-gamma (p=0.028) and IL5 (p=0.012) secretion but increased IL10 (p=0.047) on day 5, indicating that CFP is a strong stimulus for IL10 secretion in pulmonary TB patients. Extrapulmonary TB patients (E.TB; n=6) showed no elevation of early monocyte-derived cytokines to either PPD or CFP, but showed a marked suppression of the T-cell-derived cytokines IFN-gamma (PPD, p=0.015; CFP, p=0.05) and IL5 (PPD, p=0.05; CFP, p=0.015). Cytokine analysis in WB cultures is, therefore, able to discriminate between active tuberculosis infection and nondiseased healthy controls.

Item Type: Article
Keywords: cytokines, whole-blood assay, tuberculosis, pulmonary and, extrapulmonary, T-cell responses, immune-response, mycobacterium-tuberculosis, pulmonary tuberculosis, leprosy patients, skin-test, antigens, disease, activation, infection, Adolescence, Adult, BCG Vaccine, administration & dosage, immunology, Bacterial Proteins, immunology, Cells, Cultured, Comparative Study, Cytokines, biosynthesis, blood, secretion, Dose-Response Relationship, Immunologic, Female, Human, Leukocytes, Mononuclear, immunology, metabolism, Lipopolysaccharides, pharmacology, Lymphocyte Transformation, Male, Middle Age, Mitogens, pharmacology, Monocytes, immunology, metabolism, Mycobacterium tuberculosis, immunology, Pakistan, epidemiology, Phytohemagglutinins, pharmacology, Predictive Value of Tests, T-Lymphocyte Subsets, immunology, metabolism, Tuberculin, immunology, Tuberculosis, diagnosis, epidemiology, immunology, Tuberculosis, Pulmonary, diagnosis, epidemiology, immunology
Faculty and Department: Academic Services & Administration > Academic Administration
Research Centre: TB Centre
Vaccine Centre
PubMed ID: 12191514
Web of Science ID: 176472600012
URI: http://researchonline.lshtm.ac.uk/id/eprint/16454

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