Low in vitro production of interferon-γ and tumor necrosis factor-α in HIV-seronegative patients with pulmonary disease caused by nontuberculous mycobacteria

We studied 32 HIV-seronegntive patients with pulmonary disease caused by nontuberculous mycobacteria (NTM). Immunologic studies included lymphocyte subset analysis by flow cytometry, measurement of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-ol) production following in 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 foul cases with different amounts of the very mycobacterium, which caused disease in these patients. Data were compound to those of 30 HIV-seronegative patients with disease by Mycobacterium tuberculosis (MTb). Following alpha -CD3-stimulation of PBMC, NTM patients showed lower IFN-gamma (P < 0.00005) and lower TNF-<alpha> (P < 0.02). For a subgroup of tuberculin skin test-positive NTM patients we found significantly lower PPD-induccd IFN-<gamma> releases in cultured DWB (P < 0.0002) and PBMC (P < 0.0003) compared to MTb patients. Data for PPD-induced TNF-alpha release for this subgroup were also significant (P < 0.001 and P < 0.05, respectively). The four NTM patients with poor PPD-induccd IFN-gamma response hardly showed increased cytokine production on stimulation with their specific mycobacterium, The lower production capacity of IFN-gamma and TNF-alpha 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.