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Human & Experimental Toxicology
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Effects of organochlorine pesticides on interleukin secretion from lymphocytes

T M Beach

Department of Chemistry, Tennessee State University, Nashville, TN 37209, USA

M M Whalen

Department of Chemistry, Tennessee State University, 3500 John A. Merritt Blvd., Nashville, TN 37209-1561, USA; mwhalen{at}tnstate.edu

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 µM, 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 µM) and PCP (5 and 10 µM), 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.

Key Words: cytotoxicity • immunomodulation • interleukins • NK cells • organochlorine pesticides

Human & Experimental Toxicology, Vol. 25, No. 11, 651-659 (2006)
DOI: 10.1177/0960327106070072


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