ALDICARB TREATMENT INHIBITS THE STIMULATORY ACTIVITY OF MACROPHAGES WITHOUT AFFECTING THE T-CELL RESPONSES IN THE SYNGENEIC MIXED LYMPHOCYTE-REACTION

Aldicarb, a carbamate pesticide used exetensively throughout the United States, has been shown in several areas to contaminate drinking water at levels exceeding 100 p.p.b. Recent studies have suggested that aldicarb at levels well below these found in drinking water may lead to alterations in mammalian health. In the present study, we investigated the possible toxic effects of aldicarb on the mammalian immune system. Specifically examined in these studies were the effects of aldicarb on syngeneic mixed lymphocyte reaction (SMLR) in which CD4+ T-helper cells (autoreactive T-cells) respond to self or syngeneic Ia molecules expressed on macrophages. The effect of aldicarb was delineated at both the responder and stimulator cell-level. When C3H mice were injected intraperitoneally with a single dose of 0.1-1000 p.p.b. of aldicarb, it was observed that there was a decrease in the stimulatory functions of macrophages, as studied by decreased capacity to stimulate normal autoreactive T-cells. Further analysis revealed that the decreased stimulatory capacity of macrophages from aldicarb-treated mice was not due to decrease in the expression of Ia antigens, since flow cytometric analysis of macrophages from aldicarb-treated mice demonstrated normal levels of Ia expression. Also, cell-mixing experiments failed to demonstrate any suppressor macrophages in addicarb treated mice. Addition of exogenous interleukin-1, however, completely reconstituted the defective stimulatory activity of macrophages from addicarb-treated mice. In contrast to these effects on macrophages, it was observed that in C3H mice treated intraperitoneally with single dose of 1-1000 p.p.b. of aldicarb, there was no evidence of alteration in the ability of autoreactive T-cells to respond to syngenic Ia molecules expressed on normal macrophages. In addition, responsiveness of T-lymphocytes obtained from aldicarb-treated mice to Ia antigens was also unaltered. These data suggested that aldicarb may selectively suppress the stimulatory activity of macrophages by inhibiting IL-1 mediated signal to the T-cells without directly affecting the T-cell functions. © 1990.