Effect of Corynebacterium acnes on interferon production in mouse peritoneal exudate cells.

Corynebacterium acnes, an organism closely related to C. parvum, has been recognized to have a striking effect on the reticuloendothelial system, as well as on both humoral and cellular immunity. In mice previously exposed to C. acnes, serum interferon levels induced by injection of Newcastle disease virus (NDV), Chikungunya virus (CV), and polyinosinic-polycytidylic acid are suppressed. When peritoneal macrophages and lymphocytes from animals exposed to C. acnes were cultivated in vitro, their capacity to produce interferon in response to NDV and CV was reduced. Furthermore, the interferon-producing capacity of these cells in tissue culture was inhibited after exposure to C. acnes to vitro. Exposure of separated populations of peritoneal macrophages and lymphocytes to C. acnes in vitro demonstrated that the interferon response to NDV by both cell types is inhibited. Peritoneal macrophages appear to be the major contributor to the interferon response in this system. Finally, this inhibitory effect was shown to occur after exposure to a purified cell wall preparation of C. acnes organisms, as well as a lipid extract of this preparation.     

Effect of exogenous interferon on rubella virus production in carrier cultures of cells defective in interferon production

An established cell line (Vero) defective in interferon production was used to evaluate the role of interferon in chronic rubella virus infections of cell cultures. Inoculation of Vero cells with a low multiplicity of virus resulted in the development of carrier cultures which had the characteristics of a regulated infection. Although added interferon did not alter rubella virus production in carrier cultures of cells capable of producing interferon, such added interferon caused a dramatic reduction of virus production in the carrier cultures of Vero cells. There was a reduction of the fraction of cells producing virus in Vero carrier cultures, but not in carrier cultures of other cells upon incubation in the continual presence of rubella virus antibodies. In addition, the fraction of infected cells fluctuated in carrier cultures in Vero cells. The data indicate that interferon is not necessary for maintaining a chronic rubella virus infection in vitro and suggest an instability of the virus genome in Vero cells.     

Effect of simian immunodeficiency virus infection on tumor necrosis factor-alpha production by alveolar macrophages

We studied the release of tumor necrosis factor-alpha (TNF alpha), a vital immunoregulatory cytokine, by alveolar macrophages (M phi s) infected with simian immunodeficiency virus (SIV) in vitro or collected from SIV-infected macaques. For in vitro studies, M phi s were harvested by bronchoalveolar lavage from 5 normal animals and infected in flasks with SIV (10(4)TCID50/2.5 x 10(6) M phi s). After 7 to 10 days, cytopathic effect was prominent and 68 +/- 2% of M phi s were immunoreactive for p27 core protein. Uninfected (control) and SIV-infected M phi s were then cultured for 24 hours in 96-well plates (10(5) M phi s/well) while challenged with lipopolysaccharide (LPS; 100 micrograms/ml). TNF alpha was assayed in culture supernatants by an enzyme-linked immunosorbent assay (detection limit, 50 pg/ml) and results were expressed as pg TNF alpha/ml/10(3) M phi s (mean +/- SEM). TNF alpha was not detected in unstimulated wells. TNF alpha release by control and SIV-infected M phi s was similar (6.6 +/- 0.7 and 7.9 +/- 1.1 pg/ml/10(3) M phi s, respectively). We also studied TNF alpha release by alveolar M phi s from 8 animals infected with SIV (3 asymptomatic, 5 with acquired immune deficiency syndrome virus (AIDS]. One animal with AIDS had p27+ M phi s. Alveolar M phi s from asymptomatic animals released significantly more TNF alpha (10.3 +/- 1.1 pg/ml/10(3) M phi s) than did animals with AIDS or uninfected macaques (5.2 +/- 0.8 and 7.0 +/- 0.6 pg/ml/10(3) M phi s, respectively) (p less than 0.01). However, M phi s from monkeys with AIDS failed to respond to LPS after 7 to 10 days in culture. In summary, in vitro infection with SIV does not cause constitutive TNF alpha release or alter the response of cultured M phi s to LPS. When kept in culture, M phi s collected from asymptomatic, SIV-infected animals retain their response to LPS, whereas M phi s from animals with AIDS lose the capacity to produce TNF alpha. Furthermore, M phi s cytokine production is exaggerated before overt clinical disease, but not as a direct result of infection with SIV.     

Influence of L-tetramisole on the interferon production by mouse peritoneal and L929 cells.

The effect of L-tetramisole (Levamisole, Decaris) on the physiological interferon beta (INF beta) production by freshly isolated peritoneal cells of BALB/c, NZB and C3H mouse strains was studied. We have shown that these strains differ in their ability to produce physiological IFN. Peritoneal cells of individual BALB/c and NZB mice differed significantly in ability to produce the physiological IFN, but most of these animals are good producers, while the cells isolated from C3H mice are not. High concentrations of L-tetramisole (250 and 500 micrograms/ml) suppressed IFN synthesis in the cells from BALB/c and NZB mice. Lower concentration of L-tetramisole (125 micrograms/ml) inhibited the IFN production only partially and this effect was observed when the IFN production was high. When the IFN production was very low, L-tetramisole slightly increased the synthesis. L-tetramisole affected the production of the physiological IFN, but not the production of IFN induced by Newcastle disease virus (NDV) in the peritoneal cells of mice or in L929 cells.     

Three strains of influenza A virus (H3N2): interferon sensitivity in vitro and interferon production in volunteers.

Three antigenic variants of the H3N2 subtype of wild-type influenza A virus (representing the years 1968, 1972, and 1974) were examined for their sensitivity to interferon and for their ability to induce local respiratory tract interferon in volunteers. In addition, the time of appearance of symptoms in infected volunteers was correlated with the patterns of virus shedding and interferon production. The sensitivity to interferon and the ability to stimulate nasopharyngeal interferon were similarly high for all three strains. Symptomatic illness, peak virus shedding, and peak interferon response all occurred within a 26-h period. These findings imply that interferon or its inducers theoretically could be protective if applied prophylactically, but would be less efficacious when used therapeutically.     

Effect of gamma interferon on hydrogen peroxide production by cultured mouse peritoneal macrophages.

Macrophage activation is thought to be mediated via a number of T-lymphocyte products, including gamma interferon (IFN-gamma). However, our studies indicate that IFN-gamma acts as a regulator molecule rather than solely as an activator. This depends upon the status of the macrophage. IFN-gamma treatment of resting macrophages and those activated or elicited by sodium caseinate, lipopolysaccharide, or Mycobacterium bovis BCG did not result in activation, as measured by hydrogen peroxide production; however, when thioglycolate was used as an eliciting agent, incubation with IFN-gamma resulted in a dramatic increase in hydrogen peroxide production compared with that by untreated controls.     

Lack of correlation between interferon production of mononuclear cells and virus replication in chronic hepatitis B virus infection.

Interferon production in hepatitis B virus carriers with normal liver functions was preserved, whereas in carriers with chronic hepatitis it was depressed. The lower interferon production in hepatitis B virus carriers with chronic hepatitis appears to be the result rather than the cause of chronic hepatic disease.     

Synthesis of interferon in human leukocyte cells stimulated with influenza virus

Strains of influenza A virus were tested for their ability to induce interferon synthesis in suspension of human leukocytes. Both, active as well as UV-inactivated strains were shown to be weak interferon inducers as compared to Newcastle virus. It appeared that interferon synthesis in human leukocytes was conditioned not by infectivity of the virus but by the presence of its surface antigens--hemagglutinin and neuraminidase.     

Squamous metaplasia of the lung alveolar epithelium in mice after influenza virus infection.

Metaplasia of the lung alveolar epithelium was observed in mice challenged with influenza virus after previous infection, and in mice repeatedly infected. Immunological factors are suggested to contribute to the development of the process.     

Role of macrophage activation and interferon in the resistance of alveolar macrophages from infected mice to influenza virus

Lung macrophages from uninfected CD1 mice support the replication of influenza viruses (H1N1 and H0N1), but the cells from influenza-infected mice do not. The possible mechanisms of this resistance were investigated. Murine macrophages were "activated" in vitro with lipopolysaccharide and lymphokines, and in both cases activation was associated with resistance of cells to infection with influenza virus. Exposure of alveolar macrophages in vitro to 500 U of purified type I interferon per ml enhanced cell spreading and Fc receptor-mediated phagocytosis, suggesting macrophage activation, and protected the cells against infection with influenza virus. Alveolar macrophages were also protected by a soluble factor in the bronchoalveolar washings from influenza-infected mice. This effect was not virus specific and was abolished by anti-interferon serum.     

流感病毒诱导小鼠胶质细胞的细胞因子级联反应

目的:探讨流感病毒感染星形胶质细胞后释放的细胞因子是否会诱导正常胶质细胞趋化因子及促炎细胞因子转录水平的变化,从而产生细胞因子级联效应。方法:从新生小鼠大脑皮质分离培养神经胶质细胞,并进一步纯化星形胶质细胞,经纯度鉴定后,用感染复数为2的流感病毒H1N1和H3N2进行体外感染星形胶质细胞,分别于6小时和24小时收获上清,采用超滤分子截留的方法,去除流感病毒颗粒。用不同时间点的条件上清,分别刺激星形胶质细胞和小胶质细胞,24小时后提取RNA并进行反转录,利用Real-Time PCR检测促炎因子TNF-α、IL-1β、IL-6,趋化因子IP-10、MCP-1、MIP-1转录水平的变化。结果:不同时间点的条件上清皆可诱导正常胶质细胞的促炎症因子TNF-α、IL-1β、IL-6和趋化因子IP-10、MCP-1、MIP-1的转录水平发生不同程度的上调,产生细胞因子级联效应。结论:流感病毒H1N1和H3N2感染星形胶质细胞后所引起的细胞因子风暴,可诱导正常胶质细胞的细胞因子转录水平显著上调,引发细胞因子级联反应,其可能与流感病毒感染中枢神经系统所引发的细胞因子风暴及免疫病理损伤存在一定关系。     

Effect of interferon on the exogenous Friend murine leukemia virus infection

Interferon treatment (600 U/ml) of NIH/3T3 cells induced greater than 90% reduction in the de novo production of Friend MuLV when measured 24 hr postinfection. Early events in viral replication such as the synthesis of proviral DNA and its subsequent integration into the cell genome were not inhibited by interferon treatment indicating that the suppression of virus production by interferon appears to occur after synthesis of proviral DNA. Analysis of viral RNA species present in controls and interferon-treated cells 24 hr after infection show that the same RNA species were present in the presence and absence of interferon. Synthesis of viral polypeptides was reduced but not blocked in interferon-treated cells when measured within 24 hr after infection while processing of gag precursor, Pr65^gag, and glycoprotein precursor, gPr85^env, to viral proteins was not altered. Phosphorylation of viral protein p12 but not that of the precursor, Pr65^gag, was inhibited in newly infected interferon-treated cells. In contrast to the first replicative cycle, interferon did not inhibit synthesis of viral proteins, and phosphorylation of p12 in those cells chronically infected with F-MuLV.     

Effect of natural and synthetic immunomodulators on the synthesis of interferon by peritoneal cells of mice.

The effect of different natural and synthetic immunomodulators on the spontaneous interferon (IFN) synthesis by freshly isolated resident peritoneal cells of BALB/c, NZB and C3H mice was investigated. Actinomycetal glycolipids isolated from Curtobacterium betae, Faenia rectivirgula, Rothia dentocariosa and Saccharopolyspora hirsuta at the concentration 1-20 micrograms/ml were found to potentiate the IFN synthesis by the peritoneal cells of BALB/c mice. Similar results were obtained when dsRNA, LPS of Shigella sonnei and lipid A isolated from the LPS were used. The effect of potentiation of the physiological IFN production by the immunomodulators was observed also in the cells of C3H and NZB mice. In contrast, the inhibition of the IFN synthesis was observed when the peritoneal cells of BALB/c and NZB mice were treated with imuthiol at concentration 0.1-10 micrograms/ml. Thymomodulin (TFX-Polfa) at concentration of 1-100 micrograms/ml had no effect on the spontaneous IFN production.     

Effect of interferon on exogenous murine leukemia virus infection.

When interferon (IF)-treated NIH/3T3 cells were exogenously infected with the Moloney strain of murine leukemia virus (M-MLV), no viral progeny release was detected as long as IF remained in the medium. This was evidently an inhibition of the virus replication and not a consequence of interfering with the establishment of the infection since, when IF was removed either before infection or later after infection, virus release gradually approached the rate of untreated control after a temporary delay. Furthermore, a direct examination revealed that IF treatment had no effect on the formation of infectious centers. IF treatment led to a reduced viral RNA synthesis. A similar inhibition of viral RNA synthesis was observed when the potent protein synthesis inhibitor cycloheximide (CH) was added early after infection. However, when added at a late stage, the drug had no effect on viral RNA synthesis. It appears, therefore, that IF-induced inhibition of viral RNA synthesis is not a feedback consequence of an inhibition of a later step but, rather, an inhibition of some early step. This conclusion was substantiated by the finding that when IF was eliminated from pretreated cultures up to 10 hr before infection, progeny release was still affected.     

Protective essential oil attenuates influenza virus infection: An in vitro study in MDCK cells

Background  

Influenza is a significant cause of morbidity and mortality. The recent pandemic of a novel H1N1 influenza virus has stressed the importance of the search for effective treatments for this disease. Essential oils from aromatic plants have been used for a wide variety of applications, such as personal hygiene, therapeutic massage and even medical practice. In this paper, we investigate the potential role of an essential oil in antiviral activity.