Induction of macrophage membrane interleukin 1 expression by T-cell dependent and T-cell independent pathways is inhibited by cyclosporin A

Here we report that cyclosporin A (CsA) inhibits the induction of membrane interleukin 1 (mIL-1) expression on murine peritoneal macrophages. The inhibition of mIL-1 expression was noted in response to both autoreactive T-cell lines specific for class I or class II MHC determinants as well as bacterial endotoxin. The macrophages were the direct target of this inhibition as shown by pretreating T cells and macrophages separately with CsA. The effective suppression by CsA of endotoxin-induced mIL-1 expression was dependent not only on the concentration of endotoxin employed, but also on the relative time of addition of CsA and endotoxin. Furthermore, CsA pretreatment of macrophages abrogated their ability to stimulate synthesis of IL-4 by a Th2 cell clone. These data suggest that inhibition of induction of accessory molecules such as mIL-1 may be a mechanism by which CsA abrogates the capacity of macrophages to present antigen.