Y-interferon, and

Cytokine receptors that couple to the JAK-STAT Pathway decode the signaling though hematopoietic cytokines (erythropoietin, thrombopoietin, colony-stimulating factors), prolactin, growth hormone, the a-, (3- and y- interferons, and a number of immunomodulatory interleukins [3], They form homodimetic or heterodimeric receptor complexes, which after ligandbinding recruit and activate isotypes of Janus kinases (JAKs). Activated JAKs in turn... 

IL-6 expression can be activated in neutrophils upon exposure to GM-CSF and TNF, whilst IL-3, G-CSF, y-interferon and lymphotoxin do not induce expression of this cytokine. Expression of IL-6 has been identified by analysis of mRNA levels and by protein analysis. Following GM-CSF exposure, expression is detectable by 2 h, maximal by 6 h and then returns to base-line levels. LPS, PMA (but not fMet-Leu-Phe) and cycloheximide also induce IL-6 transcripts. The finding that this protein-synthesis inhibitor increases mRNA levels suggests either that transcription is regulated by a short-lived repressor, or else that decay of its mRNA may be regulated by a short-lived RNase. 

Neopterin. Neopterin is a low-molecular-weight substance derived from guanosine triphosphate (GTP) via the enzyme GTP-cyclohydrolase 1. Numerous investigators have demonstrated that neopterin, a product of human macrophages stimulated by y interferon and other cytokines, is a useful in vivo marker of the activation of cellular immunity (U4, Wl). Increased values of neopterin in body fluids have been reported in patients with malignancy, infections, and several inflammatory states. 

Causes The following causes are seen as being responsible for an acquired immune deficiency syndrome in liver cirrhosis (B.A. Runyon, 1995) (i.) hypofunction of the RES (a decrease in the filter or clearance function and phagocytosis capacity as well as reduced formation of immune modulators) (s. p. 65), (2.) reduction in hepatic synthesis of opsonins (s. p. 66), (3.) compromised function of leucocytes, (4.) impaired proliferation and activation of T lymphocytes, and (5.) increased mucosa permeability to bacteria. Both bacteria and bacterial lipopolysaccharides enter the organism in large numbers. They are responsible for increased serum levels of the cytokines (e. g. interleukins 1 and 6, TNF, y-interferon), and there is increased production of these substances together with their reduced breakdown in the cirrhotic liver. Cytokines are formed in the monocytes of blood and in the mononuclear cells of various organs (above all in ascites). 

The size distribution and density of inclusion bodies have been studied only for two proteins, calf prochymosin and y-interferon (64). The mean particle sizes of y-interferon and prochymosin inclusion bodies were O.Slgm with a standard deviation of 0.17gm and 1.28gm with a standard deviation of 0.46gm, respectively. The buoyant density of the y-interferon and prochymosin inclusion bodies was proportional to the density of the suspension medium indicating a relatively high voidage within the particles. The void fraction (=void volume/total volume) was 70% for y-interferon and 85% for prochymosin. 

Corticosteroids block cytokine activation by binding to glucocorticoid response elements, thereby inhibiting IL-1, -2, -3, and -6, y-interferon, and tumor necrosis factor a (TNF-a) synthesis (See Fig. 87-1). Additionally, steroids interfere with cell migration, recognition, and cytotoxic effector mechanisms. ... 

Zuckerman SH, Suprenant YM. Induction of endothelial cell/macrophage procoagulant activity synergistic stimulation by y interferon and granulocyte-macrophage colony stimulating factor. Thromb Haemost 1989 61(2) 178-182. 

Gaczynska M, Rock KL, Goldberg AL (1993) y-Interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature 365 264-267 Ghislain M, Dohmen RJ, Levy F, Varshavsky A (1996) Cdc48p interacts with Ufd3p, a WD repeat protein required for ubiquitin-mediated proteolysis in Saccharomyces cerevisiae. EMBO J 15 4884-4899... 

Immunochemical assays of y-interferons and serum autoantibodies (antinuclear, antimitochondrial, antiparietal antibodies of B-lymphocytes)... 

Rose, K., M. G. Simona, R. E. Offord, C. P. Prior, B. Otto, and D. R. Thatcher A New Mass Spectrometric C-terminal Sequencing Technique Finds a Similarity Between y-Interferon and a2-Interferon and Identifies a Proteolytically Clipped y-Interferon That Retains Full Antiviral Activity. Biochem. J. 215, 273 (1983). 

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