Systemic IFN (systemic + ifn)

Distribution by Scientific Domains


Selected Abstracts


Systemic IFN-, drives kidney nephritis in B6.Sle123 mice

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008
Anna-Marie Fairhurst
Abstract The impact of IFN-, secretion on disease progression was assessed by comparing phenotypic changes in the lupus-prone B6.Sle1Sle2Sle3 (B6.Sle123) strain and the parental C57BL/6 (B6) congenic partner using an adenovirus (ADV) expression vector containing a recombinant IFN-, gene cassette (IFN-ADV). A comprehensive comparison of cell lineage composition and activation in young B6 and B6.Sle123 mice revealed a variety of cellular alterations in the presence and absence of systemic IFN-,. Most IFN-,-induced phenotypes were similar in B6 and B6.Sle123 mice; however, B6.Sle123 mice uniquely exhibited increased B1 and plasma cells after IFN-, exposure, although both strains had an overall loss of mature B cells in the bone marrow, spleen and periphery. Although most of the cellular effects of IFN-, were identical in both strains, severe glomerulonephritis occurred only in B6.Sle123 mice. Mice injected with IFN-ADV showed an increase in immune complex deposition in the kidney, together with an unexpected decrease in serum anti-nuclear antibody levels. In summary, the predominant impact of systemic IFN-, in this murine model is an exacerbation of mechanisms mediating end organ damage. [source]


Mediation of nonerosive arthritis in a mouse model of lupus by interferon-,,stimulated monocyte differentiation that is nonpermissive of osteoclastogenesis

ARTHRITIS & RHEUMATISM, Issue 4 2010
Kofi A. Mensah
Objective In contrast to rheumatoid arthritis (RA), the joint inflammation referred to as Jaccoud's arthritis that occurs in systemic lupus erythematosus (SLE) is nonerosive. Although the mechanism responsible is unknown, the antiosteoclastogenic cytokine interferon-, (IFN,), whose transcriptome is present in SLE monocytes, may be responsible. This study was undertaken to examine the effects of IFN, and lupus on osteoclasts and erosion in the (NZB × NZW)F1 mouse model of SLE with K/BxN serum,induced arthritis. Methods Systemic IFN, levels in (NZB × NZW)F1 mice were elevated by administration of AdIFN,. SLE disease was marked by anti,double-stranded DNA (anti-dsDNA) antibody titer and proteinuria, and Ifi202 and Mx1 expression represented the IFN, transcriptome. Microfocal computed tomography was used to evaluate bone erosions. Flow cytometry for CD11b and CD11c was used to evaluate the frequency of circulating osteoclast precursors (OCPs) and myeloid dendritic cells (DCs) in blood. Results Administration of AdIFN, to (NZB × NZW)F1 mice induced osteopetrosis. (NZB × NZW)F1 mice without autoimmune disease were fully susceptible to focal erosions in the setting of serum-induced arthritis. However, (NZB × NZW)F1 mice with high anti-dsDNA antibody titers and the IFN, transcriptome were protected against bone erosions. AdIFN, pretreatment of NZW mice before K/BxN serum administration also resulted in protection against bone erosion (r2 = 0.4720, P < 0.01), which was associated with a decrease in the frequency of circulating CD11b+CD11c, OCPs and a concomitant increase in the percentage of CD11b+CD11c+ cells (r2 = 0.6330, P < 0.05), which are phenotypic of myeloid DCs. Conclusion These findings suggest that IFN, in SLE shifts monocyte development toward myeloid DCs at the expense of osteoclastogenesis, thereby resulting in decreased bone erosion. [source]


Systemic IFN-, drives kidney nephritis in B6.Sle123 mice

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008
Anna-Marie Fairhurst
Abstract The impact of IFN-, secretion on disease progression was assessed by comparing phenotypic changes in the lupus-prone B6.Sle1Sle2Sle3 (B6.Sle123) strain and the parental C57BL/6 (B6) congenic partner using an adenovirus (ADV) expression vector containing a recombinant IFN-, gene cassette (IFN-ADV). A comprehensive comparison of cell lineage composition and activation in young B6 and B6.Sle123 mice revealed a variety of cellular alterations in the presence and absence of systemic IFN-,. Most IFN-,-induced phenotypes were similar in B6 and B6.Sle123 mice; however, B6.Sle123 mice uniquely exhibited increased B1 and plasma cells after IFN-, exposure, although both strains had an overall loss of mature B cells in the bone marrow, spleen and periphery. Although most of the cellular effects of IFN-, were identical in both strains, severe glomerulonephritis occurred only in B6.Sle123 mice. Mice injected with IFN-ADV showed an increase in immune complex deposition in the kidney, together with an unexpected decrease in serum anti-nuclear antibody levels. In summary, the predominant impact of systemic IFN-, in this murine model is an exacerbation of mechanisms mediating end organ damage. [source]


Maternal circulating interferon-, and interleukin-6 as biomarkers of Th1/Th2 immune status throughout pregnancy

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2008
Aziz Aris
Abstract Aim:, T cells may be classified as T helper type 1 (Th1) cells, which synthesize cytokines inducing cellular immunity, or T helper type 2 (Th2), which synthesize cytokines inducing humoral immunity. According to the Th1/Th2 paradigm, it has been postulated that successful pregnancy induces an immune Th2 bias, but it is not yet clear how Th1 and Th2 systems vary simultaneously throughout the pregnancy. Methods:, Using maternal circulating interferon-, (IFN-,) and interleukin-6 (IL-6) as biomarkers of Th1 and Th2 cytokines, respectively, we examined the variation of circulating Th1/Th2 ratio in 35 healthy pregnant women from 10 to 40 weeks of pregnancy. Results:, With increasing gestational age, maternal circulating levels of IFN-, decrease, whereas those of IL-6 increase. The IFN-,/IL-6 ratio switches around the 19th week of pregnancy. Conclusions:, Our results suggest that maternal systemic IFN-, and IL-6 concentrations may be biomarkers of Th1/Th2 immune status during pregnancy. Moreover, our findings showed that contrary to the Th1/Th2 paradigm, the Th1 bias may be prevailing at the beginning of pregnancy, balanced in the middle of pregnancy and supplanted by the Th2 bias at the end of pregnancy. [source]