Protective Effect Of Interferon Research Articles

Interferon

Interferon

Antiviral properties of sterically hindered phenol derivatives

A recombinant murine interferon -β (rMuIFN-β) was used to suppress the development of skin lesions and death of mice after challenge with herpes simplex virus (HSV) type 1 (HSV-1).Depilated female BALB/c mice were inoculated intradermally with HSV-1, Hayashida strain, and were administered various concentrations of interferon (IFN) intraperitoneally 3 h later. The treatment with IFN was given once a day for 10 successive days. Under the conditions in which almost all control mice died after development of severe zosteriform skin lesions, the mortality of mice treated with IFN (8 × 105 or 8 × 104 U/mouse) was less than 50% (9/20 and 4/10, respectively), though all mice treated with a lower dose of IFN (8 × 103 U/mouse) died. Titration revealed that there was no significant suppression of virus growth by IFN in the skin or dorsal root ganglia, but it was significantly suppressed in the brain.The protective effect of IFN was enhanced when it was used in combination with human anti-HSV antibody having a neutralizing titer (NT) of 1:16. All mice treated with IFN (8 × 105 U/mouse) and antibody (NT, 1:16) survived, and only 40% of them developed slight zosteriform skin lesions. The effect of the combination was observed even when both IFN and antibody were diluted 1:10.The protective effect of IFN was also observed when athymic nude mice were used as the host. In this system, though the IFN-treated nude mice survived significantly longer than the controls, they finally died. In antibody- or acyclovir (ACV)-treated nude mice, there was also a prolongation of survival time as compared with control mice. The effect of antibody was enhanced by the addition of IFN, but IFN did not potentiate the effect of ACV.

Protective effect of interferon beta on human T cell leukaemia virus type I infection of CD4+ T cells isolated from human cord blood.

The present study shows the effect of human interferon beta (IFN beta) on the susceptibility of highly purified cord blood CD4+ T cells to infection with the human T cell leukaemia virus type I (HTLV-I). Unfractionated cord blood mononuclear cells (CBMC), or a separated CD4+ T cell subpopulation (CBCD4) were exposed to HTLV-I by cocultivation with a chronically infected virus-donor cell line. The results show that presence of proviral DNA as well as virus transcription was markedly reduced by IFN beta in both populations, indicating that this cytokine protects not only unfractionated CBMC but also purified CBCD4 cells from virus infection. Moreover IFN beta treatment caused 60%-80% inhibition of virus expression in CBCD4, assayed as the presence of virus core protein p19. This study demonstrates that IFN beta is able to inhibit HTLV-I infection of CBMC through a mechanism that does not necessarily involve cell-mediated natural or antigen-dependent immunity afforded by CBMC subpopulations distinct from targets of HTLV-I infection. Therefore it is reasonable to conclude that IFN beta has a direct protective effect on CBCD4, through induction of antiviral resistance/activity in target cells.

The protective effect of interferon against natural killing activity is not mediated via the expression of class I MHC antigens

Natural-killer cell mediated cytotoxicity (NK-CMC) is modulated by interferons both at the effector cell and at the target cell levels. Pretreatment of effector cells with interferon increases their cytotoxicity while pretreatment of target cells with interferons decreases their sensitivity to NK-CMC. Interferons are inducers of several genes including those of the major histocompatibility complex (MHC) and several earlier studies have established a circumstantial correlation between induction of class I MHC gene products and induction of resistance to NK-CMC. In the present study we demonstrate that interferon-alpha renders Daudi cells resistant to NK-CMC without inducing the surface expression of class I MHC antigens. Therefore we suggest that these two phenomena are independent responses to interferon treatment.

Protection against herpes simplex virus infection in mice by recombinant murine interferon-β in combination with antibody

A recombinant murine interferon -beta (rMuIFN-beta) was used to suppress the development of skin lesions and death of mice after challenge with herpes simplex virus (HSV) type 1 (HSV-1). Depilated female BALB/c mice were inoculated intradermally with HSV-1, Hayashida strain, and were administered various concentrations of interferon (IFN) intraperitoneally 3 h later. The treatment with IFN was given once a day for 10 successive days. Under the conditions in which almost all control mice died after development of severe zosteriform skin lesions, the mortality of mice treated with IFN (8 X 10(5) or 8 X 10(4) U/mouse) was less than 50% (9/20 and 4/10, respectively), though all mice treated with a lower dose of IFN (8 X 10(3) U/mouse) died. Titration revealed that there was no significant suppression of virus growth by IFN in the skin or dorsal root ganglia, but it was significantly suppressed in the brain. The protective effect of IFN was enhanced when it was used in combination with human anti-HSV antibody having a neutralizing titer (NT) of 1:16. All mice treated with IFN (8 X 10(5) U/mouse) and antibody (NT, 1:16) survived, and only 40% of them developed slight zosteriform skin lesions. The effect of the combination was observed even when both IFN and antibody were diluted 1:10. The protective effect of IFN was also observed when athymic nude mice were used as the host. In this system, though the IFN-treated nude mice survived significantly longer than the controls, they finally died. In antibody- or acyclovir (ACV)-treated nude mice, there was also a prolongation of survival time as compared with control mice. The effect of antibody was enhanced by the addition of IFN, but IFN did not potentiate the effect of ACV.

Protective effect of interferon on infections with hand, foot, and mouth disease virus in newborn mice.

The protective effect of interferon on infection with coxsackievirus type A 16 (CA-16) or enterovirus type 71 (EV-71) in newborn mice was examined. Subcutaneous administration of murine interferon (MuIFN-alpha/beta) into the infected mice produced a protective effect against infection with CA-16 or EV-71. It was found that the time of administration of MuIFN was important in relation to the cycle of infection. Protection was observed when MuIFN was given once daily for several days, from one day before or after infection with the lethal dose of CA-16 or EV-71. These results suggest that interferon may directly suppress infection with CA-16 and not indirectly suppress it by the medium of macrophages, natural killer cells, and T cells.

The effect of differentiation inducers on the sensitivity of two myeloid cell lines to natural killer (NK) cell-mediated lysis

The effects of differentiation inducers on the sensitivity of two human myeloid cell lines, K562 and HL-60, to natural killer (NK) cell lysis were examined. K562 cells treated with 12-O-tetradecanoyl phorbol-13-acetate (TPA) and HL-60 cells treated with either TPA or dimethylsulfoxide (DMSO) not only became less sensitive NK targets, but also became less competitive in cold target inhibition experiments. Target binding cell assays revealed that TPA-treated target cells bound fewer NK effector cells than did untreated targets. TPA treatment renders K562 and HL-60 target cells more susceptible to hypotonic lysis, indicating that the decreased NK sensitivity is not due to altered osmotic fragility. The observed reduction in sensitivity to NK lysis was not apparently mediated by interferon (IFN) released by the target cells, as neither alpha nor gamma IFN were detected in culture supernatants. Furthermore, the effects of TPA were additive to the known protective effect of IFN on NK target cells. In contrast to the parent line, a subclone of HL-60 resistant to chemically induced differentiation did not become a less sensitive target after exposure to TPA. These observations with myeloid and erythroid target cells imply that the reduced killing of the TPA-treated cells was secondary to impaired recognition of the target by the effector, and that the state of cellular differentiation is a major determinant of susceptibility to NK cell-mediated lysis.

Regulation of human natural killing. II. Protective effect of interferon on NK cells from suppression by PGE2.

Activation of human natural killer (NK) cells in vitro with interferon (IFN) and poly I:C results in a partial loss of sensitivity of these cells to suppression by PGE2. The acquired resistance to suppression can be induced with the large granular lymphocytes (LGL) in the absence of monocytes. With K562, HSB, and CEM used as NK target cells, the IFN-induced resistance to suppression by PGE2 is observed with all three target cells. Furthermore, ADCC activity of IFN-activated cells against tumor (SB-TNP) and erythroid (CRC-TNP) target cells is also less susceptible to suppression by PGE2. The dual effect of IFN on NK cells is prompt; the augmentation of NK activity and the acquired resistance to suppression by PGE2 can be seen after 3 hr of treatment with IFN. Both of these characteristics seem to be quite stable for at least 24 hr. Spleen cells from mice (CBA, C3H, and BALB/c nude) treated in vivo with poly I:C also acquire partial resistance to suppression by PGE2. Our data therefore suggest that IFN-stimulated NK cells are protected from suppression by PGE2. Biologically, the IFN-induced protective effect may be beneficial to host resistance to neoplasia.

Protective effect of low-dose interferon against neonatal murine cytomegalovirus infection.

Mice were injected with 10 to 5,000 reference units of interferon intraperitoneally or subcutaneously within 24 h of birth and reinoculated intraperitoneally 24 h later with 200 plaque-forming units of murine cytomegalovirus. Mock interferon and virus diluent were the control inocula. Infection of mock interferon-treated mice resulted in significant retardation of growth, accompanied by tissue injury and a depressed blastogenic response of splenic lymphocytes. Prophylactic administration of interferon prevented growth retardation and resulted in lower tissue viral titers and diminished injurious effects of the virus. Intraperitoneal inoculation of interferon was more protective than was subcutaneous, and 10 U of interferon was often as effective as 5,000 U. Accelerated maturation and enhanced activity of lymphoid elements were observed histologically in spleens and lymph nodes of interferon-treated mice; supportive of these findings was the greater incorporation of [3H]thymidine of splenocytes from interferon-treated mice. The protective effect of interferon may, therefore, be due to stimulation or accelerated maturation of cellular immune functions.

Protective Effects of Interferon in Mice Previously Exposed to Lethal Irradiation

The radioprotective action of interferon (IF) in increasing the survival time of mice lethally irradiated 24 h previously was evaluated. A single intraperitoneal injection of 30,000 units of IF administered 1 day following a LD/sub 100/ dose of irradiation significantly prolonged the mean survival time of the animals. Multiple inoculations of IF given 1,3, and 5 days after irradiation only slightly increased the survival time over that observed in mice receiving single injections. Marked decreases in total number of splenocytes were observed in irradiated mice as well as in the mice receiving postirradiation IF therapy, whereas total peripheral white blood cell counts were not appreciably changed when evaluated 3 days after X irradiation. Natural lymphocyte killer activity of splenocytes from irradiated animals receiving IF was significantly increased, suggesting that the protective action of IF could be partially attributable to the boosting of some depressed immune functions.

Studies on the capacity of human tonsillar lymphocyte subpopulations to produce interferon.

Tonsillar lymphocytes produced classical interferon (Type I) in response to NDV infection and produced immune interferon (Type II) in response to PHA, PPD or histo-incompatible antigens. Lymphocytes having higher specific gravity and having a greater proliferative response to mitogens or antigens produced more interferon than lymphocytes having lower specific gravity. There was no difference between heavy and light small tonsillar lymphocytes in regard to their sensitivity to the protective effects of interferon. As for the interferon produced in association with a cellular immune response, the peak of interferon production tended to appear earlier than the peak of 3H-TdR incorporation. It is suggested that tonsillar lymphocytes play an important role in human host defense against virus infections.

Mengovirus-induced cytopathic effect in L-cells: protective effect of interferon.

The effect of interferon on mengovirus-induced cytopathic effect (CPE) in L cells, the cut-off of host-cell protein synthesis, and production of mature virus were found to be dependent on the concentration of interferon. CPE and inhibition of host protein synthesis were not affected until the concentration of interferon was increased 100-fold over that required to reduce viral yields by 90%.

Protection of Mice Against Aerosol-transmitted Influenza A2 Virus Infection by Stimulation of Interferon

There are many reports in the literature indicating that the administration of exogenous interferon or induction of endogenous interferon can protect experimental animals against certain virus infections (reviewed by Finter, 1966, and Vilcek, 1969). In most of these studies, challenge was by parenteral inoculation of relatively large quantities of virus and the protective effects of interferon were assessed in terms of decreased mortality or less severe disease. However, naturally acquired virus infection is generally the consequence of exposure to much smaller quantities of virus, and with respiratory viruses, infection is initiated by deposition of virus in appropriate areas of the respiratory tract and not by parenteral inoculation. Accordingly, experiments were designed to determine whether interferon induced by Newcastle disease virus (NDV) could protect mice from infection by influenza virus transmitted by other mice. This experimental system was described in detail by Schulman & Kilbourne (1963) and was used to study the effects on transmission of infection of other modifications of the host such as immunization (Schulman, 1967).

The effect of interferon on focus formation and yield of murine sarcoma virus in vitro.

SummaryInterferon-treated cells yielded less murine sarcoma virus and were less susceptible to focus formation than were untreated cells or cells treated with control mouse serum. The protective effect of interferon appeared to be lost or at least significantly reduced 24 hr after treatment.

Protective effect of interferon and polyacrylic acid in newborn mice infected with a lethal dose of vesicular stomatitis virus

Abstract Repeated intraperitoneal doses of preformed interferon and a single intraperitoneal injection of polyacrylic acid were shown to protect newborn mice from lethal infection with vesicular stomatitis virus. Both survival time and number of surviving mice were considerably increased by the injections. The antiviral activity of interferon and polyacrylic acid was inversely proportional to the dose of challenge virus. Nearly 100% of the mice treated with interferon survived a nearly 100% lethal infection (16 LD50). Polyacrylic acid diminished the mortality rate by 50 %. It is concluded that polyacrylic acid induces good host resistance to viruses and may be suitable in the prophylaxis of virus infections in vivo.

Protective effect of interferon in influenza-infected mice

Protective effect of interferon in influenza-infected mice