Neutralization of TNF-α is more detrimental to iNOS^−/− than WT mice.

<p>TNF-α neutralization leads to increased influx of activated cells to the lungs, increased mortality and non-organized lesions in iNOS-deficient mice. WT and iNOS^−/− mice were treated with anti-TNF-α mAb (MP6 XT 22) or normal rat IgG (control) and i.t. infected with 1×10⁶ fungal cells. Number and activation of lymphocytes (A) and mononuclear phagocytes (B) present in pulmonary lesions at the 2^nd week postinfection of anti-TNF-α treated and untreated mice were determined by flow cytometry. (C) Survival times of anti-TNF-α treated and untreated mice. TNF-α depleted iNOS^−/− mice showed a decreased survival time, which was significantly different (* <i>P</i><0.05) from all other studied groups. The results are representative of three independent experiments (n = 6–7). (D) Photomicrographs of pulmonary lesions developed by IgG-treated (D, superior panels) and TNF-α-depleted (B, lower panels) mice at the week 8 of infection. Anti-TNF-α treatment of iNOS-deficient mice resulted in less organized, fungi rich, confluent lesions, occupying the largest part of lung tissue. H&E stained lesions (100×).