Disease relevance of Polyriboinosinic-polyribocytidylic acid

• Conversely, iNOS-deficient mice were not resistant to the antiviral effect of IFN-alpha/beta induced by either polyinosinic-polycytidylic acid complex or by lymphocytic choriomeningitis virus (LCMV) infection [1].
• NK activity against both targets is stimulated 3 d after injection of Corynebacterium parvum, and 24 h after challenge with polyinosinic:polycytidylic acid [2].
• Polyriboinosinic-polyribocytidylic acid (poly I - poly C), an interferon inducer, was administered in multiple doses of 0.3-75 mg/m2 to 26 patients with a variety of solid tumors, 9 with acute leukemia, and 2 with chronic myelogenous leukemia in blast crisis [3].
• When virus type IFN (IFN-alpha/beta) inducers, Newcastle disease virus, polyriboinosinic-polyribocytidylic acid, 10-carboxymethyl-9-acridanone, and E. coli endotoxin, were administered to mice, no change in IFN response was observed after thermal injury [4].
• Furthermore, treatment of mice with Poly I:C strongly reduces the metastatic capacity of 3LL-R tumor cells, suggesting the participation of macrophages in the eradication of the established metastasis [5].

Psychiatry related information on Polyriboinosinic-polyribocytidylic acid

• Poly I:C decreased spontaneous motor activity (SMA) 2 h after i.p. administration, and this decrease was maintained thereafter [6].
• Although poly rI:rC treatment reduced the proportional urinary excretion of each of the thio adducts the individual differences were not significant [7].
• Poly I:C increased slow-wave sleep duration, suppressed rapid-eye-movement sleep, and induced fever but failed to raise plasma Cu [8].

High impact information on Polyriboinosinic-polyribocytidylic acid

• Human NK-cell activity can be augmented in vitro by interferon and its inducers, including polyinosinic:polycytidylic acid (poly I:C); furthermore, NK-like activity is generated in mixed leukocyte cultures (MLCs) as is specific cytotoxic T-cell (Tc) activity [9].
• Moreover, both known inducers of interferon (poly I:poly C) and standard preparations of interferon are capable of enhancing histamine release [10].
• Two lysosomotrophic drugs, neutral red and chloroquine, enhance polyinosinic:polycytidylic acid-induced interferon production by a strain of diploid human fibroblasts (FS-4) [11].
• Kinetics of depression and recovery of murine hepatic cytochrome P-450 levels after treatment with the interferon inducer polyriboinosinic-polyribocytidylic acid [12].
• In contrast, polyinosinic:polycytidylic acid strongly represses CpG's as well as its own intrinsic ability to induce PDGF-B mRNA through type I IFN-mediated induction of Smad7, a negative regulator of Smad3/4 [13].

Chemical compound and disease context of Polyriboinosinic-polyribocytidylic acid

• Spleen cells from mice treated with statolon or chlorite-oxidized oxyamylose statolon but not Newcastle disease virus or poly rI:poly rC were resistant to immunodepression in vitro by FV leukemic spleen cells [14].
• The therapeutic efficacy of polyriboinosinic-polyribocytidylic acid stabilized with poly-L-lysine and carboxymethyl cellulose [poly(ICLC)] given alone or in combination with ribavirin was evaluated in Swiss Webster mice infected with Rift Valley fever virus [15].
• This depression in the urinary excretion of thio adducts following poly rI:rC treatment is discussed in relation to possible implications for paracetamol toxicity [7].
• Ethanol decreases natural killer cell activation but only minimally affects anatomical distribution after administration of polyinosinic:polycytidylic acid: role in resistance to B16F10 melanoma [16].
• The non-responder state of mice to Mycobacterium vaccae by i.p. route of immunization could be corrected by prior treatment with poly I:poly C, an interferon inducer, or indomethacin, a prostaglandin inhibitor [17].

Biological context of Polyriboinosinic-polyribocytidylic acid

• Poly I:C enhancement of NK-mediated natural resistance in the lung, liver, and peritoneal cavity was also abolished by IFN pretreatment [18].
• We previously identified a disease-susceptibility locus in the BBDR rat, iddm4, which is associated with the development of autoimmune diabetes after treatment with polyinosinic:polycytidylic acid and an antibody that depletes ART2(+) regulatory cells [19].
• Poly IC induced islet cell Class I hyperexpression, up regulation of pancreatic endothelial intercellular adhesion molecule-1 and vascular adhesion molecule-1 and a T-cell and macrophage infiltration of the pancreatic interstitium in all rat strains studied, including diabetes-resistant strains [20].
• Poly IC also induced the generation of diabetes-transferring spleen cells in most Class II(u) haplotype rats, including the diabetes-resistant WF rat [20].
• Production of interferon-beta upon induction with polyinosinic acid:polycytidylic acid during the cell cycle of human fibroblasts [21].

Anatomical context of Polyriboinosinic-polyribocytidylic acid

• To examine whether dsRNA and CpG DNA could combine to provide enhanced stimulation of innate immune cells, murine macrophages were stimulated with poly-rI:rC (pIC), a dsRNA analog, and CpG-containing oligodeoxynucleotides (CpG-ODN) [22].
• The inhibitory activity was seen even with 0.2 ml of the 10,000-fold dilution of the fluid and with its filtrate passed through a Diaflo UM-10 membrane (greater than 10,000-dalton exclusion), However, such tumor ascitic fluids did not affect the induction of type I interferon in mice by polyriboinosinic-polyribocytidylic acid or tilorone-HCl [23].
• Coisogenic diabetes-resistant (DR) BB/Wor rats do not develop diabetes spontaneously, but IDDM can readily be induced by treatment with polyinosinic:polycytidylic acid and depletion of RT6+ T-cells [24].
• The effects of polyinosinic:polycytidylic acid (pI:C) on the graft-vs-host (GVH) reaction. II. Increased NK-mediated rejection on C57BL/6 lymphocytes by (C57BL/6 X A)F1 mice [25].
• Human monocytes were cultured for 24 h in serum-free AIM-V medium, followed by 24-h maturation by polyriboinosinic polyribocytidylic acid (polyI:C) [26].

Associations of Polyriboinosinic-polyribocytidylic acid with other chemical compounds

• A combination CS consisting of a novel taste (saccharin) and a 125 mg/kg injection of LiCl that induces gastric upset was paired with a Poly I:C or IFN-beta (1 X 10(4) IU) injection [27].
• Stabilization of polyriboinosinic-polyribocytidylic acid against enzymatic hydrolysis by addition of poly-1-lysine and carboxymethylcellulose (PICLC) resulted in a compound with marked adjuvanticity [28].
• A nuclease-resistant complex of polyriboinosinic-polyribocytidylic acid containing poly-L-lysine and carboxymethylcellulose was used as prophylactic treatment of simian hemorrhagic fever in rhesus monkeys [29].
• We previously demonstrated that Poly (IC) decreased the growth of C6 cultures in association with reduced IGF-I synthesis and secretion [30].
• Polyinosinic acid:polycytidylic acid induced significantly higher amounts of IFN but lower levels of TNF and IL-6 than imiquimod [31].

Gene context of Polyriboinosinic-polyribocytidylic acid

• Poly I:C also induces the novel capability of producing CXCL10 chemokine in human NK cells and synergistically enhances interferon-gamma (IFN-gamma) production induced by either adaptive or innate cytokines [32].
• Treatment of mice with the chemical IFN inducer, polyinosinic:polycytidylic acid, has a similar effect [33].
• Our results revealed that while NK cell depletion and elimination of IFN-gamma partially protected against the sensitizing effects of vesicular stomatitis virus and polyinosinic:polycytidylic acid, the most striking effect was observed in IFN-alphabetaR-deficient mice [33].
• To explore the spectrum of genes induced in human astrocytes by TLR3, we used a microarray approach and the analog polyriboinosinic polyribocytidylic acid (pIC) as ligand [34].
• The induction is stimulated by treatment of the cells with interleukin 1 (IL 1) (alpha or beta) or polyriboinosinic-polyribocytidylic acid [poly(rI).poly(rC)] [35].

Analytical, diagnostic and therapeutic context of Polyriboinosinic-polyribocytidylic acid

• To investigate the role of innate immunity, mice given costimulation blockade and skin allografts were coinjected with TLR2 (Pam3Cys), TLR3 (polyinosinic:polycytidylic acid), TLR4 (LPS), or TLR9 (CpG) agonists [36].
• Poly IC + IFN-gamma stimulates iNOS expression and inhibits insulin secretion by primary beta-cells purified by fluorescence-activated cell sorting [37].
• We previously demonstrated that treatment of (C57BL/6 X A)F1 (F1) recipient mice with polyinosinic:polycytidylic acid (pI:C) before injection with 30 X 10(6) C57BL/6 (B6) lymphocytes prevents both the immunosuppression and pathologic lesions typical of graft-vs-host (GVH) reactions [25].
• In DP rats, all anti-CD2 MAb prevented spontaneous diabetes and the adoptive transfer of diabetes with Con-A--stimulated acute diabetic spleen cells; OX34 prevented Poly I:C induced accelerated onset of diabetes and the adoptive transfer of diabetes with Con-A--stimulated RT6.1+ T cell depleted DR splenocytes [38].
• Mouse interferon induced by ultraviolet-irradiated Newcastle disease virus or polyriboinosinic-polyribocytidylic acid in T lymphocytes, B lymphocytes, macrophages, and primary mouse embryonic cell culture was studied [39].

References