Deoxynivalenol-induced cytotoxicity, cytokines and related genes in unstimulated or lipopolysaccharide stimulated primary porcine macrophages

The cytotoxicity of deoxynivalenol (DON) as well as the induction of cytokines and related genes was investigated in porcine pulmonary alveolar macrophages (PAM) in absence or presence of lipopolysaccharides (LPS). IC20 Values were 1.1, 0.4 and 1.0 mu M DON in the MTT, neutral red and alamar blue assay. respectively, and did not differ significantly in the presence of LPS. The mRNA expression of tumour necrosis factor (TNF)-alpha peaked at 3 h, whereas LPS and DON showed synergistic effects resulting in an approximately 20-fold increase at 500 nM DON as compared to Untreated controls. The supernatant concentrations of TNF-alpha showed similar synergistic effects. The expression of interleukin (IL)-1 beta was significantly induced by DON (except for 12 h) and UPS. An induction of the mRNA expression of IL-6 by DON was evident only at 3 h, Whereas the supernatant concentrations of LPS stimulated PAM incubated with 500 nM DON were significantly decreased at most time points. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression did not seem to contribute to the effects of DON in porcine macrophages. The results of the present investigation suggest a Contribution of cytokines, especially TNF-alpha and IL-1 beta, induced by DON in porcine macrophages to the effects observed in vivo. (C) 2008 Elsevier Ireland Ltd. All rights reserved.