Activation of alpha-human tumour necrosis factor (TNF-alpha) by human monocytes (THP-1) exposed to 2-chloroethyl ethyl sulphide (H-MG).

Tumour necrosis factor (TNF) is a monokine produced by monocytes and macrophages in response to different stimuli. To determine whether vesicant agents such as half-mustard gas (H-MG; chemical structure: ClCH2CH2SCH2CH3) may induce the release of TNF-alpha in human monocytes (THP-1), ELISA experiments were conducted at different post exposure times. The results indicate that: (1) Significant increases in the TNF-alpha (pg mL-1) concentration were observed as a function of time when THP-1 cells were exposed to 100 microL of 2 M H-MG. A specific serine-type protease inhibitor, N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), led to partial but significant inhibition of TNF activation. (2) Furthermore, this laboratory detected the generation of spin adducts of 2-methyl-2-nitrosopropane (MNP) having a resemblance to MNP-adducts generated from hydrogen atom abstraction of protein constituents. The EPR/Spin Trapping data indicate the trapping of by-products of protein degradation after exposure to H-MG. TNF-alpha may play a role as a biochemical marker for pathophysiological changes induced by H-MG or related agents.