Effects of nickel sulfate on pulmonary natural immunity in Wistar rats

This study was designed to investigate the in vivo effect of nickel sulfate on the pulmonary non-specific immune defences. Groups of four male Wistar rats were treated with a single intratracheal instillation of NiSO4 at diff erent doses: 1, 2, 4 and 8 mu mol of NiSO4 per rat. Control rats received a corresponding instillation of the saline vehicle. The effect of NISO, on t he cytotoxic activity of the pulmonary natural killer (NK) cells and alveol ar macrophages (AM), as well as the pulmonary production of cytokines such as alpha-tumor necrosis factor (TNF-alpha) and gamma-interferon (IFN-gamma) , were examined 1, 2 and 7 days later. Spontaneous NK-cytotoxicity towards mouse-derived tumor cell line, Yac-l was suppressed 1 day after treatment a t doses of 2 mu mol/rat and above with only one result significant (P < 0.0 5); 2 days after treatment the suppression was increased with all results s ignificant at the same doses; 1 week after treatment NK activity restoratio n was observed except for the highest dose, 8 mu mol/rat. AM-mediated cytot oxicity towards mouse-derived tumor cell line, 3T12, did not show any signi ficant difference in treated and untreated animals. In contrast, whereas mo derate levels of TNF-alpha were detected in the broncho-alveolar lavage (BA L) fluid supernatants of controls, the NISO4 treatment highly suppressed TN F-alpha production with a maximum observed after 2 days. TNF-alpha suppress ion was found to be transient, at least with the lowest NiSO4 dose, with le vels returning to normal after 7 days. A non-significant increase in IFN-ga mma was observed in the BAL fluids of treated animals at each time of exami nation. Taken together, these results indicate that NK cell activity and TN F-alpha secretion are sensitive targets for instilled NiSO4 in Wistar rats. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.