Induction of murine interleukin 1: stimuli and responsive primary cells.

Abstract

An interleukin 1.alpha. (IL-1.alpha.) cDNA probe and an IL-1 responsive T-cell clone (D10.G4; half-maximal stimulation, 0.1-1 pM) have been used to study the production of IL-1 by primary murine cell populations, particularly macrophages and dendritic cells. Spleen and peritoneal macrophages produced IL-1 mRNA and released biologically active IL-1 when challenged with lipopolysaccharide (LPS). Induction of IL-1 was evident over a dose range of 0.01-10 .mu.g of LPS per ml, and maximal mRNA levels were maintained from 4 to 20 hr. Several other stimuli did not induce IL-1 in cultured macrophages, including phorbol 12-myristate 13-acetate, .gamma.-interferon, Con A, macrophage colony-stimulating factor, IL-3, cachectin, and activated T cells. Activated T cells could markedly reduce the response of peritoneal macrophages to LPS. When other cell types were compared with macrophages, keratinocytes had high levels of IL-1 mRNA, apparently in response to endogenous LPS. However B and T lymphocytes did not yield detectable IL-1 during proliferative responses to LPS and Con A, respectively, while dendritic cells produced little of no IL-1 when challenged with a battery of stimuli. Therefore, IL-1 may not be required for the potent accessory function of dendritic cells in lymphocyte mitogenesis. The results indicate that macrophages and dendritic cells have different secretory capacities. The macrophage is the principal leukocyte that synthesizes IL-1, and select stimuli increase and decrease the levels of macrophage IL-1 mRNA.