Interferon: An Inducer of Macrophage Activation by Polyanions

Schultz, Richard M.; Papamatheakis, Joseph; Chirigos, Michael A.

doi:10.1126/science.877584

Cited by 252 publications

(61 citation statements)

References 26 publications

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“…This induction may be followed by activation of macrophages (17) and augmentation of NK activity through the action of the induced IFN (2). A recent report, how-ever, states that GL is also effective against alcoholic hepatitis (9).…”

mentioning

confidence: 99%

Interferon Induction by Glycyrrhizin and Glycyrrhetinic Acid in Mice

Abe

Ebina

Ishida

1982

Microbiology and Immunology

202

104

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Licorice extract is an herbal drug which has long been used as a demulcent and elixir in Chinese medicine. One of the main active components of licorice extract is glycyrrhizin (GL), a kind of saponin. The biological effects of GL and its aglycone, glycyrrhetinic acid (GA), have been extensively studied. Their anti-inflammatory (5), anti-ulcerous (3), and antiviral (14) effects have been reported from 1948 (15) to 1979 (14). Moreover, a preparation of GL combined with glycine and cysteine (SNMC), has been widely and successfully used in Japan as an antihepatitis drug (6, II, 19), although its mechanism of pharmacological action remains unclear.Recently, interferon (IFN) with or without adenine arabinoside (Ara-A) has been used to treat hepatitis B patients (4, 7). Studies show that IFN consistently decreases the level of either DNA polymerase or hepatitis B surface antigen in hepatitis patients. There are also many reports which suggest that some irnmunopotentiators induce IFN (13) and explain their antiviral activity in vivo as interferon mediated (8,16,18). Therefore, in the light of GL's clinical effect on hepatitis patients and of the fact that its structure resembles that of hydrocortisone, the possibility that GL induces IFN was proposed. In this study we investigated the ability of both GL and GA to induce IFN in mice.Six-to 8-week-old male DDI mice obtained from the Institute for Experimental Animals, Tohoku University School of Medicine, were used in this experiment. Six-week-old male C3H, ddY, CDF-l, C57BL, BALB/c, and athymic nude mice (nujnu) of BALB/c background were obtained from the Funabashi Farm Co., Ltd., and were used to study the effect of the different mouse strains on interferon induction.GL and GA were supplied by Minophagen Pharmaceutical Co. Drugs were dissolved in 0.01 M phosphate buffered saline (PBS) and adjusted to pH 7.2 with I N sodium hydroxide.Pooled sera obtained from three mice were tested for anti-viral activity, which was determined by the 50% plaque reduction method on L-929 monolayer cell cultures with vesicular stomatitis virus (VSV) and was expressed in international reference units based on NIH reference mouse IFN (Catalog No. 002-904-511) (12).

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mentioning

confidence: 99%

Interferon Induction by Glycyrrhizin and Glycyrrhetinic Acid in Mice

Abe

Ebina

Ishida

1982

Microbiology and Immunology

202

104

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“…Cumulative evidence indicates that, among their diverse properties, interferons may have a regulatory influence on several immune functions: suppression of lymphocyte proliferation in response to mitogens and alloantigens (LindahlMagnusson et al, 1972a); inhibition in vivo and in vitro of antibody formation to T-cell-dependent and independent antigens (Braun & Levy, 1972;Gisler et al, 1974;Johnson et al, 1975;Sonnenfeld et al, 1977) and enhancement of specific cell-mediated cytotoxicity evoked by tumour-and allo-antigens (Lindahl et al, 1972b;Heron et al, 1976;Zarling et al, 1978). Interferon may also stimulate other effector-cell-mediated mechanisms such as phagocytosis (Huang et al, 1971;Donahoe & Huang, 1976) and nonspecific cytotoxicity (Schultz et al, 1977;Einhorn et al, 1978;Djeu et al, 1979;Senik et al, 1979), act directly on various cell types to inhibit their growth in vitro (Stewart et al, 1976;Balkwill et al, 1978) and modulate the expression of cell surface antigens on lymphocytes and tumour cells (Vignaux & Gresser, 1977).…”

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confidence: 99%

Enhancement of human natural cell-mediated cytotoxicity by interferon

Moore¹,

Potter²

1980

Br J Cancer

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Summary.-The effect of exogenous Namalva interferon (IF) on the natural killer (NK) cell activity of human blood lymphocytes was examined against 5 target cell lines (K562, CCRF/CEM, Molt 4, Raji and Bri8) using the 51Cr-release assay. Addition of IF to the test significantly increased the cytotoxicity, though not as much as when effector cells were treated with IF before the test. Augmentation of cytotoxicity was evident after only 1 h pretreatment and was maximal by 6 h. The rate of lysis of susceptible targets by IF-treated effectors markedly exceeded that by their untreated counterparts. Separation of lymphocyte subpopulations (by SRBC-rosette sedimentation and nylon-fibre column filtration) demonstrated that the activities of IF-stimulated and unstimulated cells were similarly distributed, suggesting that the major effect of IF is enhancement of the activity of pre-existing NK cells rather than generation of new populations of effectors. Target cell lines with high and low susceptibility to NK cells showed increased cytotoxicity by IF-treated effector cells. These findings may be relevant to the current discussion of the role of NK cells in immunosurveillance against neoplasia.

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“…Moreover, we showed in preliminary experiments that natural killer (NK) cell activity in both splenocytes and peritoneal exudate cells derived from SSM-treated mice is higher than in cells from normal control mice. Furthermore, it was reported by Schultz et al (30)(31)(32) that the antitumor activity shown by interferon was mediated by the macrophages activated by the interferon. In addition it was shown by Cantor et al (5) that NK cells may play an important role in prevention of neoplastic growth in hosts.…”

Section: Characterization Of Antiviral Actioity Induced By Ssmmentioning

confidence: 98%

Interferon‐Inducing Activity of an Immuno‐therapeutic Anticancer Agent, SSM, Prepared from Mycobacterium tuberculosis Strain Aoyama B

Hayashi

Ebina

Suzuki

et al. 1981

Microbiology and Immunology

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The interferon-inducing capacity of arabinornannan-lipid preparation (SSM) extracted from Mycobacterium tuberculosis Aoyama B in both BCG-sensitized and unsensitized mice was studied in comparison with that of purified protein derivative (PPD) prepared from the same tubercle bacillus. Although it is known that PPD cannot stimulate interferon production in BCG-unsensitized mice, interferon activity was found in sera of both groups of mice after intravenous injection of SSM at a dose of 5 mg/kg. The maximum titer was detected 5 hr after injection. The interferon induced by SSM in both groups of mice shared certain physicochemical properties with the immune interferon induced by PPD in BCGsensitized mice. In BCG-unsensitized mice, interferon induction by SSM was markedly inhibited by pretreatment with trypan blue and carrageenan, whereas it was not depressed in BCG-sensitized mice given the same treatment or when interferon was induced by PPD. In addition, induction of interferon in BCGsensitized mice by SSM and PPD and in unsensitized mice by SSM was completely abrogated by pretreatment with hydrocortisone acetate and whole-body x-irradiation (700 R). These results suggest that in BCG-unsensitized mice macrophages, in addition to X-ray or hydrocortisone-sensitive cells, may be required for interferon induction by SSM.

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Interferon: An Inducer of Macrophage Activation by Polyanions

Cited by 252 publications

References 26 publications

Interferon Induction by Glycyrrhizin and Glycyrrhetinic Acid in Mice

Interferon Induction by Glycyrrhizin and Glycyrrhetinic Acid in Mice

Enhancement of human natural cell-mediated cytotoxicity by interferon

Interferon‐Inducing Activity of an Immuno‐therapeutic Anticancer Agent, SSM, Prepared from Mycobacterium tuberculosis Strain Aoyama B

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