Macrophage activation for the production of immunostimulatory cytokines by delivering interleukin 1 via biodegradable microspheres

Interleukin 1α (IL-1α), a pleiotropic cytokine with multiple anti-tumour activities, has been investigated in our laboratory for its potential to serve as an immunotherapeutic agent. In the present study, an attempt was made to direct IL-1α to macrophages, in order to induce their immunoregulatory activities. For that purpose, IL-1α was encapsulated within biodegradable poly(lactic/glycolic acid) microspheres, 1-5 μm diameter in size. The microspheres were efficiently taken-up by macrophages in culture and after intraperitoneal injection into mice. In culture, phagocytosis of the microspheres reached saturation within 3 h and there was no apparent effect of polymer type on the extent of uptake. In vivo uptake of human IL-1α-microspheres by the macrophages lead to cell activation, as evidenced by the enhanced production of murine IL-1α, IL-6 and IL-12. Control microspheres, containing bovine serum albumin, induced only background to low levels of cytokine production. These cytokines, when expressed by or secreted from macrophages, may stimulate in situ diverse immune and inflammatory responses, including T cell-mediated immune responses, such as the development of Th₁ cells and cytotoxic lymphocytes. Thus, directing IL-1α into macrophages, via the appropriate microspheres, may serve as a unique mean to activate these cells to participate in anti-tumour immune responses in situ. (C) 2000 Academic Press.