Biomaterial Database

IFN-gamma-independent production of IL-12 during murine endotoxemia. 1996

F P Heinzel, and R M Rerko, and F Ahmed, and A M Hujer

Division of Geographic Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.

We examined whether IFN-gamma deficiency alters the in vivo IL-12 response occurring in the mouse model of acute endotoxemia. C57BL/6 IFN-gamma knockout mice (IFN-gamma 0/0) produced as much circulating IL-12 p40 and IL-12 p70 as did IFN-gamma +/+ mice following injection with S. enteritidis LPS, despite sustaining 11-fold reductions in circulating TNF-alpha. Pretreatment of IFN-gamma 0/0 mice with recombinant mouse IFN-gamma (rIFN-gamma) enhanced circulating TNF-alpha by as much as sixfold, but serum IL-12 p40 and IL-12 p70 responses increased by only twofold or less. Compared with IFN-gamma +/+ mice, the spleens of endotoxemic IFN-gamma 0/0 mice generated two- to threefold fewer IL-12 p40-secreting cells following in vitro or in vivo exposure to endotoxin. The addition of rIFN-gamma to IFN-gamma 0/0 splenocyte culture restored normal levels of LPS-stimulated IL-12 p40 production. Removal of Mac-1+ or F4/80+ cells from endotoxin-stimulated spleen reduced both TNF-alpha and IL-12 p40 production, but 33D1+ dendritic cell removal only affected IL-12 synthesis. These data suggest that the aggregate IL-12 p40 and p70 response to endotoxemia in vivo is IFN-gamma-independent and distinct from IFN-gamma-dependent serum TNF-alpha and splenic IL-12 responses. The cellular and/or cytokine basis for the unexpected preservation of IL-12 production in IFN-gamma-deficient mice may be relevant to normal and pathologic immune responses.

UI	MeSH Term	Description	Entries
D007371	Interferon-gamma	The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.	Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D005260	Female		Females
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013154	Spleen	An encapsulated lymphatic organ through which venous blood filters.
D014409	Tumor Necrosis Factor-alpha	Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.	Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345	Mice, Knockout	Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.	Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out
D018664	Interleukin-12	A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.	Edodekin Alfa,IL-12,Natural Killer Cell Stimulatory Factor,Cytotoxic Lymphocyte Maturation Factor,IL 12,IL-12 p70,IL12,Interleukin 12,Interleukin-12 p70,Interleukin 12 p70