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.