Interferon (IFN) has been shown to have a profound effect on tumor growth, viral replication, and the immune response. This study addresses two important mechanisms by which the IFN system is regulated. The first mechanism involves the cooperative interaction of different IFNs when they are employed in combination. This potentiation occurs for both mouse and human systems when IFN-Gamma is mixed with IFN-Alpha or IFN-Beta. Mixtures of IFN-Alpha and IFN-Beta do not show potentiation. Potentiation provides a 10- to more than 200-fold greater than expected level of IFN activity based on the additivity of the IFNs. This tremendous increase in IFN activity has been noted for both in vivo and in vitro antitumor systems as well as in vitro antiviral systems. A variety of viruses, tumors, and cell lines will be employed. This study will more carefully quantitate the potentiation phenomenon, seek to elucidate the mechanisms by which potentiaton occurs, and evaluate potentation for possible clinical application. The second mechanism of IFN regulation involves an inhibitor of IFN action which is produced by mitogen-stimulated mouse and human leukocytes. This inhibitor blocks the antiviral, anticellular, and immunoregulatory activity of IFN. This study will employ inhibitor produced and purified in bulk quantities so it may be characterized and employed to study the modulation and control of the antitumor and antiviral activities of IFN.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA026475-05
Application #
3167326
Study Section
Experimental Immunology Study Section (EI)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Fleischmann, C M; Fleischmann Jr, W R (1991) Resistance to the antiproliferative activity of IFN-alpha: further characterization and demonstration of antagonistic effects of IFN-gamma. J Biol Regul Homeost Agents 5:34-42
Fleischmann Jr, W R; Fields, E E; Wang, J L et al. (1991) Modulation of peripheral leukocyte counts in mice by oral administration of interferons. Proc Soc Exp Biol Med 197:424-30
Kotnik, V; Fleischmann Jr, W R (1990) A simple and rapid method to determine hematopoietic growth factor activity. J Immunol Methods 129:23-30
Fleischmann Jr, W R; Ramarathinam, N; Fields, E E (1990) Effects of phenytoin on the production of interferons: differential effects on type I and type II interferons. J Biol Regul Homeost Agents 4:107-16
Fleischmann, C M; Fleischmann Jr, W R (1988) Effects of hyperthermia on the in vitro antiproliferative activities of HuIFN-alpha, HuIFN-beta, and rHuIFN-gamma employed separately and in combination. J Biol Regul Homeost Agents 2:145-54
Fleischmann, C M; Fleischmann Jr, W R (1988) Differential antiproliferative activities of IFNs alpha, beta and gamma: kinetics of establishment of their antiproliferative effects and the rapid development of resistance to IFNs alpha and beta. J Biol Regul Homeost Agents 2:173-85
Ramamurthy, V; Fleischmann Jr, W R (1988) Regulation of MuIFN-alpha/beta and MuIFN-gamma-induced antiviral states: differential effects with different challenge viruses and lack of correlation with 2'5' oligoadenylate synthetase levels. J Biol Regul Homeost Agents 2:7-14
Naldini, A; Fleischmann Jr, W R (1987) In vivo myelosuppression by combination interferon treatment: antagonism of MuIFN-gamma and MuIFN-beta myelosuppressive effects. J Biol Response Mod 6:546-55
Naldini, A; Fleischmann Jr, W R; Ballas, Z K et al. (1987) Interleukin 2 inhibits in vitro granulocyte-macrophage colony formation. J Immunol 139:1880-4
Koren, S; Fleischmann Jr, W R (1986) Quantitation of in vivo potentiation resulting from combined interferon therapy: antitumor effect against B-16 melanoma in mice. J Interferon Res 6:473-82

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