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

We studied 32 HIV-seronegntive patients with pulmonary disease caused by no ntuberculous mycobacteria (NTM). Immunologic studies included lymphocyte su bset analysis by flow cytometry, measurement of interferon-gamma (IFN-gamma ) and tumor necrosis factor-alpha (TNF-ol) production following in vitro st imulation of diluted whole blood (DWB) and peripheral blood mononuclear cel ls (PBMC) by phytohemagglutinin (PHA), anti-CD3 as well as purified protein derivative of tuberculin (PPD), and in foul cases with different amounts o f the very mycobacterium, which caused disease in these patients. Data were compound to those of 30 HIV-seronegative patients with disease by Mycobact erium tuberculosis (MTb). Following alpha -CD3-stimulation of PBMC, NTM pat ients 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 sig nificantly lower PPD-induccd IFN-<gamma> releases in cultured DWB (P < 0.00 02) and PBMC (P < 0.0003) compared to MTb patients. Data for PPD-induced TN F-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 th eir specific mycobacterium, The lower production capacity of IFN-gamma and TNF-alpha of NTM patients compared to the MTb patients points to an immunol ogic imbalance forming the basis For their increased susceptibility to pulm onary infections by nontuberculous mycobacteria.