Suppression of interleukin-1 action by phospholipase-A2 inhibitors in helper T lymphocytes.

The mechanism by which interleukin 1 (IL-1) and T cell receptor (TCR) activation co-stimulate T helper (Th) cells is not clear. In chondrocytes, fibroblasts and several other cell types, much of the evidence suggests a linkage between IL-1 action and increased phospholipase-A2 (PLA2) activity. Although Th cells have very low levels of PLA2, they are well known targets for IL-1. We studied the effects of PLA2 inhibitors, i.e., lipocortin-1 (LC-1) and the synthetic peptide antiflammin-P2 (AF-2), on the enhancing effect of IL-1 upon activation of TCR. When murine D10.G4.1 Th2 cells were stimulated by their clonotypic anti-TCR antibody 3D3, both LC-1 and AF-2 inhibited the biological response to IL-1. This blockade was not seen when D10 cells were induced to proliferate with interleukin-2 (IL-2) and 3D3 in the presence of the same inhibitors, LC-1 or AF-2. These results strongly suggest that PLA2 also plays a central role in mediating the actions of IL-1 in the helper T cell.