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Biomedical subjects

I Gresser

Publications and source records attributed to I Gresser.

At least 109 records · Page 6Linked to original sources
PubMed1982

Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. I.

Interferon-sensitive (745) and interferon-resistant (3C1-8) Friend leukemia cells (FLC) are highly tumorigenic for DBA/2 mice. The phenotype of interferon sensitivity or resistance does not change with in vivo passage. Daily administration of mouse interferon markedly enhanced the survival time of mice injected with either 745 or 3C1-8 cells. Use of quantitative methods for determining the number of FLC (colony formation in agarose and immunofluorescence) permitted us to show that potent, partially purified or highly purified mouse interferon (s.a. 0.5 to 1 X 10(9) u/mg protein) induced a 100- to 1,000-fold decrease in the number of tumor cells in the peritoneal cavity in the days following inoculation of 745 or 3C1-8 cells. Interferon decreased the number of FLC even when treatment was initiated at a time when tumor cells were multiplying exponentially in the peritoneal cavity. There was no evidence that interferon acted as an inducer of FLC differentiation in vivo. The finding that interferon was equally effective in mice inoculated with interferon-resistant cells as in mice inoculated with interferon-sensitive cells suggests that in this experimental system interferon does not act directly on the tumor cells, but that the interferon-induced antitumor activity is mediated by the host.

Animals↗
PubMed1982

Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. II. Role of host mechanisms.

We have attempted to determine what host mechanisms are responsible for inducing a rapid decrease in the number of Friend leukemia cells (FLC) in the peritoneal cavity of interferon-treated mice. By injecting radiolabelled FLC, we showed that there was a greater loss of radioactivity from individual interferon-treated mice than from control mice. Thus, it was likely that fewer cells were recovered from the peritoneal cavity of interferon-treated mice because of cell destruction. Treatment of mice with interferon limited to the period preceding tumor-cell inoculation conferred some degree of antitumor activity, although this regimen was far less effective than when interferon treatment was initiated and continued daily after tumor-cell inoculation. We have been unable to transfer any antitumor activity with peritoneal washings containing macrophages and lymphocytes from interferon-treated donor mice to tumor-inoculated recipient mice. Inoculation of silica particles i.p., which destroys macrophage function and may affect NK cell activity, did not abrogate interferon's antitumor activity. We suggest that interferon induces a host-mediated antitumor effect by mechanisms which are not mediated by easily recoverable soluble factors or by cytotoxic cells. The nature of this potent interferon-induced host mechanism remains unknown.

Animals↗
PubMed1982

Reversibility of the transformed and neoplastic phenotype. III. Long-term treatment with electrophoretically pure mouse interferon leads to the progressive reversion of the phenotype of X-ray transformed C3H/10T1/2 cells.

Electrophoretically pure mouse interferon induced the progressive reversion of the transformed phenotype of a clone of X-ray transformed C3H/10T1/2 cells. Cells of this clone did not harbor C-type particles and reverse transcriptase activity was not detected. Interferon-treated transformed cells were aligned without cellular overlapping and attained low cell densities. Morphologic changes were associated with the appearance of a thick layer of submembranous microfilaments. The tumorigenicity of interferon-treated cells was markedly reduced. Back reversion to the transformed phenotype occurred progressively when these cells were passaged in the absence of interferon. These results suggest that interferon may induce the reversion of the transformed phenotype by a mechanism other than by its antiviral activity.

Animals↗
PubMed1982

How does interferon inhibit tumour growth?

Interferon can inhibit tumour growth in experimental animals and in some patients with benign and malignant tumours. There is experimental evidence to suggest that several mechanisms may be involved: a direct effect on the tumor or an indirect effect via the host, or both. Thus, interferon may slow the rate of tumour cell multiplication and this may lead to cell death. Interferon may induce changes in the cell surface rendering tumour cells more sensitive to host defence mechanisms. Interferon may induce reversion in the phenotype of tumour cells. Interferon may stimulate specific and non-specific humoral and cellular host mechanisms. The relative importance of these different effects of interferon may vary depending on the host and the particular tumour.

Animals↗
PubMed1982

Interferon inhibits the generation of allospecific suppressor T lymphocytes.

The effect of human interferon alpha on the differentiation of functional populations of lymphocytes during the human allogeneic response in vitro was studied. Interferon alpha inhibited the generation of allospecific suppressor T lymphocytes that normally develop from lymphocytes primed in vitro against allogeneic cells. This effect was not the result of the destruction by interferon of precursor suppressor cells but rather to inhibition of their differentiation into active suppressor T lymphocytes. This inhibition was reversible and could be overcome by repeated allogeneic stimulation even in the presence of interferon. Inhibition of the generation of allospecific suppressor lymphocytes by interferon might play an important role in the allogeneic response. Interferon inhibited the proliferation of lymphocytes after allogeneic stimulation in a primary mixed lymphocyte reaction but enhanced their cytotoxicity. Despite the inhibitory effect in the primary mixed lymphocyte reaction, the specific secondary proliferative response of lymphocytes primed against a single HLA-DR antigen was only slightly affected by interferon. On the other hand, the nonspecific secondary proliferative response of lymphocytes primed in the presence of interferon was significantly reduced, indicating that interferon might decrease the recruitment of nonspecific "irrelevant" clones of responding cells during the sensitization period.

Cytotoxicity, Immunologic↗
PubMed1982

Severity of glomerulonephritis induced in different strains of suckling mice by infection with lymphocytic choriomeningitis virus: correlation with amounts of endogenous interferon and circulating immune complexes.

Renal lesions due to neonatal infection with lymphocytic choriomeningitis virus were studied in three different strains of mice known to produce different amounts of viral interferon. Very severe ultrastructural lesions similar to those induced by exogenous interferon were found as early as day 8 in C3H mice which produced the highest amount of interferon. Further studies could not be performed in these mice since all died by day 14. Balb/c mice produced the lowest amount of interferon and had very mild ultrastructural lesions. An intermediate pattern was found in Swiss mice. After 30 days of infection, severe immune complex type glomerulonephritis detectable by light microscopy and immunofluorescence was observed in Swiss mice whereas mild lesions only were found in Balb/c mice. Circulating immune complexes were present in both strains but in greater amounts of Swiss than Balb/c mice. These results suggest that two factors at least are important in the development of glomerulonephritis: interferon produced early in life and the load of circulating immune complexes.

Animals↗
PubMed1982

Stability of the phenotypic reversion of x-ray transformed C3H/10T1/2 cells depends on cellular proliferation after subcultivation at low cell density.

Reversion from the transformed to the non-transformed phenotype could be obtained by seeding X-ray transformed C3H/10T1/2 cells at low cell density. Cloned revertant cells of varying degrees of reversion were obtained depending on the time they were isolated after on subculture at low cell density. Most of the revertants isolated 7 and 10 days after seeding at very low cell density eventually returned to the transformed phenotype when passaged serially at high cell density. In contrast, 25-35% of the revertants isolated 17-20 days after seeding at low cell density maintained the non-transformed phenotype despite subsequent serial passages at high cell density. The finding that there was a direct relationship between the time during which transformed cells seeded at low cell density multiplied and the number of stable revertant clones obtained, suggests that possibility that reversion from the transformed to the non-transformed phenotype may be a multistep process. Revertant cells displayed a chromosomal pattern characteristic of the transformed cells rather than that of the parental non-transformed 10T1/2 cells.

Animals↗
PubMed1982

The role of interferon in the resistance of C57BL/6 mice to various doses of herpes simplex virus type 1.

C57BL/6 (B6) mice are relatively resistant to infection with herpes simplex virus type 1 (HSV-1). Paradoxically, B6 mice were resistant to 250 LD50 (50% lethal dose) of HSV-1 but were killed by 25 or 2.5 LD50 of HSV-1 injected intraperitoneally. At the injection site 250 LD50 of virus induced high titers of interferon (IFN) (greater than 1,000 international units) that reached maximal levels 2-4 hr after inoculation, whereas 25 or 2.5 LD50 of HSV-1 generated only borderline levels of IFN (15-40 international units). Simultaneous inoculation of 250 LD50 of HSV-1 and antiserum to mouse IFN (MuIFN) rendered B6 mice susceptible to infection; however, treatment with antiserum to MuIFN did not increase susceptibility to 1 LD50 of virus. Injections of MuIFN given 2 hr before and 2 hr after inoculation with virus protected B6 mice against 25 LD50 of virus. Thus, endogenous IFN induced after injection with 250 LD50 of HSV-1 protects B6 mice, whereas low doses of virus kill the animals because they do not generate a detectable IFN response at the infection site.

Animals↗
PubMed1982

Interferon enhances the expression of epstein-Barr virus early antigen in Daudi cells.

Treatment of the Burkitt lymphoma-derived cell line Daudi with highly purified human interferon-alpha (IFN-alpha) increased up to 100-fold the number of cells expressing Epstein-Barr virus (EBV)-determined early antigen (EA) without inducing the synthesis of virus capsid antigen (VCA), a late virus function. The increase in the number of EA-positive cells was proportional to interferon concentration up to 10(4) international units (IU)/ml. Treatment of Daudi cells with the same number of units of either partially purified (sp. act. 10(6) IU/mg protein) or electrophoretically pure (sp. act. 2 x 10(8) IU/mg protein) IFN-alpha both gave a similar increase in EA expression, strongly suggesting that the effects observed were indeed due to interferon. Furthermore, treatment of relatively interferon-insensitive Raji cells with IFN-alpha (1 to 10(4) IU/ml) had no significant effect on either spontaneous or 5-iodo-2'-deoxyuridine (IdUrd)-induced expression of EA or VCA. Human IFN-beta also enhanced the expression of EBV EA in Daudi cells. In contrast, when the latent EBV present in Daudi cells was activated to enter into a replicative cycle, either by induction with IdUrd or by superinfection with the non-transforming P3HR1 strain of EBV, then treatment with human IFN-alpha caused a marked inhibition of EA expression. Our results suggest that interferon can exert a differential action on virus replication depending upon the state of the virus genome within the cell.

Antigens, Viral↗
PubMed1982

Indomethacin and aspirin do not inhibit the antiviral or anti-proliferative actions of interferon.

Neither indomethacin nor aspirin, at concentrations which inhibited the formation of prostaglandins and prevented the interferon-induced increase in the intracellular concentration of cyclic GMP, had any significant effect on the development of the interferon-induced antiviral state either in mouse L1210 cells challenged with vesicular stomatitis virus or in mice infected with encephalomyocarditis virus. Furthermore, neither drug had any significant effect on the interferon-induced inhibition of cell multiplication in cultures of mouse leukaemia L1210 cells. The differences in the effects of these cyclo-oxygenase inhibitors on different interferon effects may provide some insight into the different pathways of interferon action.

Animals↗
PubMed1982

Interferon as a cause of endoplasmic reticulum abnormalities within hepatocytes in newborn mice.

An ultrastructural examination of livers from newborn mice, injected with potent partially purified or highly purified mouse interferon or with lymphocytic choriomeningitis (LCM) virus, has revealed the presence of tubular aggregates associated with the granular endoplasmic reticulum in the cytoplasm of hepatocytes after either treatment. Thus the lesion was observed in A2G and Swiss mice after interferon injections. It was also seen in C3H mice after LCM infection, the liver being examined at a time when the interferonaemia in the injected mice was known to be at its peak. The aggregate resembles the tubular systems associated with the endoplasmic reticulum described in various tissues in both human and animal diseases. These observations raise the possibility that in some of the cases previously described the lesion has been interferon induced.

Animals↗