Abstract

Significant advances have been made concerning the characterization of interferon (IFN): the major species have been classified, genes coding for IFN have been identified, and a number of monoclonal antibodies have been developed. However, before the most effective therapeutic applications of IFN can be designed, more information concerning IFN activity in vivo is required. These studies can most effectively be performed in animals. Based on the need for in vivo experimentation with IFN and the availability of monoclonal antibodies to murine IFN, the proposed study will: 1) isolate large quantities of pure species of natural induced murine IFN-Alpha and IFN-Beta using monoclonal antibodies; 2) determine the antigenic and functional relationships of these IFN species in vitro; 3) establish and compare the in vivo effectiveness of pure murine IFN subspecies to regulate immune responsiveness and alter tumor growth; and 4) define the mechanism of these IFN-mediated effects. Particular emphasis will be placed on investigation of the ability of murine IFN to inhibit lymphocyte recirculation since this effect may be pivotal in determining whether IFN will inhibit or enhance immune responses. The mechanism of the increase in circulating natural killer cell activity in the presence of a decrease in the total number of circulating cells will also be established. These studies will provide information concerning the mechanism of IFN activity in vivo that is essential for realization of the clinical potential of IFN immunotherapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043386-09
Application #
3185615
Study Section
Immunobiology Study Section (IMB)
Project Start
1980-05-01
Project End
1990-04-30
Budget Start
1988-05-01
Budget End
1990-04-30
Support Year
9
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Allegheny University of Health Sciences
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19129

  Publications

Kirschmann, D A; He, X; Murasko, D M (1994) Inhibition of macrophage-induced, antigen-specific T-cell proliferation by poly I:C role of suppressor macrophages. Immunology 82:238-43
Markovic, S N; Murasko, D M (1993) Anesthesia inhibits interferon-induced natural killer cell cytotoxicity via induction of CD8+ suppressor cells. Cell Immunol 151:474-80
Markovic, S N; Knight, P R; Murasko, D M (1993) Inhibition of interferon stimulation of natural killer cell activity in mice anesthetized with halothane or isoflurane. Anesthesiology 78:700-6
Kirschmann, D A; Murasko, D M (1992) Effect of exogenous cytokines on the inhibition of macrophage-induced, antigen-specific T cell proliferation by poly(I:C). Clin Immunol Immunopathol 65:300-7
Markovic, S N; Murasko, D M (1991) Role of natural killer and T-cells in interferon induced inhibition of spontaneous metastases of the B16F10L murine melanoma. Cancer Res 51:1124-8
Markovic, S N; Murasko, D M (1991) Inhibition of induction of natural killer activity in mice by general anesthesia (Avertin): role of interferon. Clin Immunol Immunopathol 60:181-9
Markovic, S N; Murasko, D M (1990) Anesthesia inhibits poly I:C induced stimulation of natural killer cell cytotoxicity in mice. Clin Immunol Immunopathol 56:202-9
Markovic, S N; Murasko, D M (1990) Neoadjuvant immunotherapy with interferon of the spontaneously metastasizing murine B16F10L melanoma. Int J Cancer 45:788-94
Mann, E A; Markovic, S N; Murasko, D M (1989) Inhibition of lymphocyte recirculation by murine interferon: effects of various interferon preparations and timing of administration. J Interferon Res 9:35-51
Skicki-Mullen, M B; Markovic, S N; Murasko, D M (1989) Interferon-induced inhibition of Moloney sarcoma virus-transformed cells: requirement for T-cells. Cancer Res 49:522-7

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