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

Abstract

An interleukin 1a (IL-1a) cDNA probe and an IL-l responsive T-cell clone (D1O.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 ,jg of LPS per ml, and maxmal 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, r-interferon, Con A, macrophage colony-stimulating factor, IL-3, cachectin, and activated T cells. Activated T cells could markedly reduce the response ofperitoneal 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 or 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.

Comparison of the Accessory Activity of Murine Peritoneal Cavity Macrophage Derived Dendritic Cells and Peritoneal Cavity Macrophages in a Mixed Lymphocyte Reaction.

“…In contrast, other studies have shown that macrophages can increase the sensitivity of MLR to Peyer's patch cells [27]. It is most likely that this effect may be mediated by macrophages production of IL-1 which is not produced by DC [16], but which amplifies DC function [15] and all these factors require further experimental analysis. Although it has been reported in previous studies that an allogeneic MLR can occur without the involvement of IL-1 [23], it is likely that all T cell responses require a number of co-stimulatory factors [11].…”

“…Variations in levels of cytokine production in the epidermis and the intestine may account for the differences in maturity of DC at the two sites. Both IL-1 and GM-CSF, which have been reported to amplify DC function [15] are produced by cells of the human intestinal tissues [30], but levels have not been compared with those of the epidermis. Peritoneal cavity macrophage derived-DC from p30 transgenic mice demonstrated greater allogeneic MLR stimulatory activity when incubated with T cells from inbred BALB/c mice at all three responder:stimulator ratios and time points.…”

The induction of cell-associated and secreted IL-1 by iscoms, matrix or micelles in murine splenic cells

“…Highly purified splenic B or T cells do not produce stL-1 in response to stimulation with iscoms, while peritoneal cells produce IL-1 upon iscom treatment in vivo (manuscript in preparation). The production of IL-1 in LPS or cholera toxin-stimulated murine cells is mediated by macrophages [7,27], and the production of IL-1 by peritoneal macrophages, cultured with heat-killed bacteria as antigen, was enhanced by addition of T cell products [28].…”

Evaluation of innate immune stimulating activity of polysaccharides using a silkworm (Bombyx mori) muscle contraction assay

“…Activity of immunostimulants for innate immunity has been evaluated based on the induction of cytokine production and phagocytosis by mammalian macrophages (28,29). Because LPS from Gram-negative bacteria are active in these assays at extremely low concentrations, the effects of LPS derived from contaminated bacteria in samples is a serious problem for evaluating immunostimulation.…”