Methyl-parathion and organophosphorous pesticide metabolites modify the activation status and interleukin-2 secretion of human peripheral blood mononuclear cells

Organophosphorous (OP) compounds are the most commonly used pesticides. There are reports on susceptibility to the toxic effects of OP pesticides, but no information exists regarding the toxicity of their metabolites. To determine the metabolites' contribution to the OP pesticide immunotoxic effects, human peripheral blood mononuclear cells (PBMCs) were treated with the parent compound methyl-parathion (MP) and the following OP pesticide alkyl-phosphorous metabolites: diethylphosphate (DEP), diethylthiophosphate (DETP), diethyldithiophosphate (DEDTP), dimethylphosphate (DMP), and dimethyldithiophosphate (DMDTP). Activation and function of the PBMCs were examined by assessment of phytohemagglutinin (PHA)-induced proliferative response, interleukin-2 (IL-2) secretion, and CD25 and CD69 expression. Treatments with DMP, DEP, DETP and DEDTP for 48 h produced significant toxicity in human PBMCs, but did not affect their proliferative response to PHA. Only MP reduced cell proliferation by 30%. DEDTP decreased the proportion of PBMCs expressing CD25. This effect was associated with a reduction of IL-2 secretion, which was also reduced by MP and DMP treatments. In contrast, DETP and DEDTP treatments increased the expression of CD69. DMP, DETP and DEDTP were more consistently involved in modulating the PBMC response to PHA.