title: Effects of organochlorine pesticides on interleukin secretion from lymphocytes.
abstract: Organochlorine pesticides have been used worldwide primarily as insecticides. Due to their chemical stability, they often persist in the environment long after their use has ceased. In a previous study, we found that six organochlorine compounds (alpha-chlordane, gamma-chlordane, 4,4'-DDT, heptachlor, oxychlordane, and pentachlorophenol (PCP)), at concentrations of 5 microM, were able to significantly decrease the ability of highly purified human natural killer (NK) cells to lyse tumor cells after exposures, ranging from 1 hour to 6 days. However, if T cells were present with the NK cells (T/NK cells), loss of lytic function was seen only with oxychlordane and PCP. The purpose of the current study is to begin to investigate the mechanism by which T cells may be blocking the negative effects of some organochlorine compounds on NK cell function. Here, we investigated the hypothesis that T cells could produce significant levels of NK-stimulatory interleukin(s) (ILs), and that this may account for the decreased inhibition seen with organochlorine exposures when T cells were present. Secretion of four cytokines that have a demonstrated capacity to influence NK function, and/or are secreted by T cells, was measured (IL-2, IL-4, IL-10, IL-12). We measured both the baseline levels of ILs and the effects of organochlorine compound on IL secretion in T/NK cells. The results showed that baseline levels of the NK-stimulatory IL, IL-12, were 898 +/- 264 pg/mL at 24 hours and IL-10 levels were 564 +/- 337 pg/mL. In contrast, IL-2 levels were 14 +/- 10 pg/mL, and IL-4 levels were 3 +/- 2 pg/mL at 24 hours. The two compounds that retained their capacity to decrease NK lytic function in T/NK cells, oxychlordane (5 microM) and PCP (5 and 10 microM), were able to either decrease the secretion of NK-stimulatory ILs (IL-2, IL-12 and/or IL-10) and/or increase secretion of the NK-inhibitory cytokine, IL-4, at each length of exposure tested.
authors.affiliation: Department of Chemistry, Tennessee State University, Nashville, TN 37209, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Beach
authors.forename: M M
authors.initials: MM
authors.lastname: Whalen
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010575:Pesticides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D006843:Hydrocarbons, Chlorinated; D007378:Interleukins; D010575:Pesticides