title: Inhibition of interleukin 2 driven proliferation of mouse CTLL2 cells, by selected carbamate and organophosphate insecticides and congeners of carbaryl.
abstract: The anticholinesterase (antiCHE) insecticides, a large family of pesticides used extensively throughout the world, inhibit serine hydrolases by carbamylating or phosphorylating a serine residue at the catalytic site. These insecticides are viewed as potential inhibitors of serine hydrolase-dependent immune functions including interleukin 2 (IL2) signalling. Previous studies in our laboratory have demonstrated that carbaryl (an antiCHE insecticide) produces a marked concentration-dependent inhibition of IL2 driven 1) proliferation of mouse CTLL2 cells, 2) proliferation of human natural killer (NK) cells, and 3) enhancement of target cell killing by human NK cells. In the present study, we examined the potential of 8 antiCHE insecticides (4 carbamates and 4 organophosphates) to inhibit IL2-dependent proliferation of mouse CTLL2 cells. The order of potency for T cell inhibition was carbaryl = dichlorvos > methiocarb > carbofuran > paraoxon > mevinphos > aldicarb = monocrotophos. In view of the relatively high inhibitory potency of carbaryl (a carbamate with low cholinergic toxicity), 3 metabolites and 5 congeners of carbaryl were tested for potency to inhibit CTLL2 proliferation. The data indicate a significant contribution of the 1-naphthol leaving group to inhibition of T cell proliferation by carbaryl, and are consistent with inhibition of a serine hydrolase(s) as a mechanism contributing to the observed inhibition of IL2-dependent proliferation.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha 68198-6025.
authors.forename: G P
authors.initials: GP
authors.lastname: Casale
authors.forename: J L
authors.initials: JL
authors.lastname: Vennerstrom
authors.forename: S
authors.initials: S
authors.lastname: Bavari
authors.forename: T L
authors.initials: TL
authors.lastname: Wang
mesh_terms: D000818:Animals; D012721:Carbaryl / Q000031:analogs & derivatives / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D006867:Hydrolases / Q000037:antagonists & inhibitors; D007306:Insecticides / Q000737:chemistry / Q000633:toxicity*; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D009943:Organophosphorus Compounds; D051381:Rats; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D007306:Insecticides; D007376:Interleukin-2; D009943:Organophosphorus Compounds; D006867:Hydrolases; D012721:Carbaryl