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Low In Vitro Production of Interferon-γ and Tumor Necrosis Factor-α in HIV-Seronegative Patients with Pulmonary Disease Caused by Nontuberculous Mycobacteria

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Abstract

We studied 32 HIV-seronegative patients with pulmonary disease caused by nontuberculous mycobacteria (NTM). Immunologic studies included lymphocyte subset analysis by flow cytometry, measurement of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production followingin vitro stimulation of diluted whole blood (DWB) and peripheral blood mononuclear cells (PBMC) by phytohemagglutinin (PHA), anti-CD3 as well as purified protein derivative of tuberculin (PPD), and in four cases with different amounts of the very mycobacterium, which caused disease in these patients. Data were compared to those of 30 HIV-seronegative patients with disease byMycobacterium tuberculosis (MTb). Following α-CD3-stimulation of PBMC, NTM patients showed lower IFN-γ(P < 0.00005) and lower TNF-α(P < 0.02). For a subgroup of tuberculin skin test-positive NTM patients we found significantly lower PPD-induced IFN-γ releases in cultured DWB(P < 0.0002) and PBMC(P < 0.0004) compared to MTb patients. Data for PPD-induced TNF-α release for this subgroup were also significant(P < 0.001 andP < 0.05, respectively). The four NTM patients with poor PPD-induced IFN-γ response hardly showed increased cytokine production on stimulation with their specific mycobacterium. The lower production capacity of IFN-γ and TNF-α of NTM patients compared to the MTb patients points to an immunologic imbalance forming the basis for their increased susceptibility to pulmonary infections by nontuberculous mycobacteria.

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Authors and Affiliations

  1. Medizinische Klinik, Forschungszentrum Borstel, Borstel, Germany

    Ulf Greinert & Max Schlaak

  2. Nationales Referenzzentrum f¨ur Mykobakterien, Forschungszentrum Borstel, Borstel, Germany

    Sabine Rũsch-Gerdes

  3. Abteilung f¨ur Immunologie und Zellbiologie, Forschungszentrum Borstel, Borstel, Germany

    Hans-Dieter Flad & Martin Ernst

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  1. Ulf Greinert
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  2. Max Schlaak
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  4. Hans-Dieter Flad
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  5. Martin Ernst
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Greinert, U., Schlaak, M., Rũsch-Gerdes, S. et al. Low In Vitro Production of Interferon-γ and Tumor Necrosis Factor-α in HIV-Seronegative Patients with Pulmonary Disease Caused by Nontuberculous Mycobacteria. J Clin Immunol 20, 445–452 (2000). https://doi.org/10.1023/A:1026407815946

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