Interleukin-1 potentiates antigen-mediated arachidonic acid metabolite formation in mast cells

Mast cells were isolated from human lung tissues using density gradient centrifugation and a fluorescence-activated cell sorter. Purified cells were sensitized passively with serum from allergic patients sensitive to grass pollen and then challenged with antigen (grass pollen). When these cells were challenged with antigen, LTC4, and PGD2 (19 +/- 6, and 42 +/- 9 pmol/10(6) cells, respectively) were released during 2 hr of incubation. When mast cells were incubated with interleukin-1 (IL-1) no detectable amount of LTC4 or PGD2 was generated. However, when mast cells were challenged with antigen and IL-1, LTC4 and PGD2 were released (60 +/- 15 and 97 +/- 21 pmol/10(6), respectively) after a 2 hr incubation period. The stimulatory action of IL-1 was both time- and dose-dependent (over a 10-1000 units/ml range). In addition, greater activity was observed if IL-1 was added 5-30 min prior to the antigen. Inhibitors of arachidonic acid metabolic pathways prevented the release of LTC4 and PGD2 from mast cells activated with antigen and IL-1. This study shows that IL-1 does not stimulate arachidonic acid metabolite release by mast cells but potentiates the release induced by antigen.