Immunomodulator Effects on the Friend Virus Infection in Genetically Defined Mice

Sidwell, Robert W.; Morrey, John D.; Okleberry, Kevin M.; Burger, Roger A.; Warren, Reed P.

doi:10.1111/j.1749-6632.1993.tb35904.x

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…5). Previous studies reported long-term therapies (12 to 25 days) for FV infection or murine AIDS in which IFN-␣ had an effect on virus replication (13,34,35). We were able to show that a short-term postexposure therapy with IFN-␣ during acute infection induced an antiviral status sufficient to control virus replication and disease progression.…”

Section: Discussionsupporting

confidence: 56%

Effects of Type I Interferons on Friend Retrovirus Infection

Gerlach

Schimmer

Weiß

et al. 2006

J Virol

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Section: Discussionsupporting

confidence: 56%

Effects of Type I Interferons on Friend Retrovirus Infection

Gerlach

Schimmer

Weiß

et al. 2006

J Virol

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“…Immune status was restored in AIDS and steroid-induced immunocompromised patients (34). Furthermore, imexon prevented the development of large cell lymphoma in animal models, reversed lymphadenopathy and splenomegaly, restored immunocompetence, and prolonged survival in a murine AIDS model (35)(36)(37)(38)(39)(40). Imexon has been shown recently to inhibit sensitive myeloma cell lines, at clinically achievable concentrations (11,41).…”

Section: Discussionmentioning

confidence: 97%

Imexon-Induced Apoptosis in Multiple Myeloma Tumor Cells Is Caspase-8 Dependent

Evens

Prachand

Shi

et al. 2004

Clinical Cancer Research

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Purpose: Imexon is a 2-cyanoaziridine agent that has been shown to inhibit growth of chemotherapy-sensitive myeloma cells through apoptosis with decreased cellular stores of glutathione and increased reactive oxygen species (ROS). We examined the mechanism of imexon cytotoxicity in a diverse panel of dexamethasone and chemotherapysensitive and -resistant myeloma cell lines.Experimental Design: We examined cellular cytotoxicity, apoptosis, and changes in redox state in dexamethasonesensitive (C2E3), dexamethasone-resistant (1-310 and 1-414), chemotherapy-sensitive (RPMI-8226), and chemotherapy-resistant (DOX-1V and DOX-10V) myeloma cell lines.Results: We found significant cytotoxicity after 48-h incubation with imexon (80 -160 M) in dexamethasone and chemotherapy-sensitive and -resistant myeloma cell lines in a time-and dose-dependent manner. The mechanism of imexon cytotoxicity in all cell lines was related to induction of apoptosis with the presence of cleaved caspase-3. Moreover, after imexon exposure in C2E3 and 1-414 cell lines, we demonstrated caspase-8-dependent apoptosis. Bcl-2:bax was proapoptotic with imexon in C2E3, whereas bcl-2:bax was independent of steroid resistance, chemotherapy sensitivity, and chemotherapy resistance. Depletion of intracellular glutathione was documented in RPMI-8226 at high imexon concentrations (>225 M) but not in other cell lines. Furthermore, ROS were found in C2E3, RPMI-8226, and 1-310 only at high imexon concentrations, whereas a sensitive marker of oxidative DNA damage, 8-hydroxydeoxyguanosine, was not increased in any cell line.Conclusions: Our results demonstrate that imexon has significant broad antimyeloma activity that is mediated through apoptotic mechanisms that is not dependent on production of ROS. Moreover, we have identified a mechanism of cytotoxicity in dexamethasone-sensitive and -resistant myeloma cells induced by imexon that is caspase-8 dependent.

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“…IFNS are significant inhibitors of murine retrovirus disease (15)(16)(17) . The antiviral efficacy may be allributable lo both more traditional antiviral effects, as noted above , and their actions as immunomodulators.…”

Section: Table L Cytokines Studied For Efficacy Against Experimentally Induced Virus Infectionsmentioning

confidence: 99%

Cyotkines as Potential Therapies for Human Immunodeficiency Virus Infections

Sidwell¹,

Morrey²,

Warren³

1994

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Cytokines are attracting increased interest as potential therapies for human immunodeficiency virus (HIV) infections. This attraction has particularly arisen as these cytokines have become more commercially available through recombinant technologies. This review focuses on the effects of these biological response modifiers on preclinical HIV and related retrovirus infections. Cytokines that have particularly been considered for HIV disease control include: interferons -α , -β and -γ, interleukins-2. -3. -4. -6 and -7; tumour necrosis factors -α and -β; and the colony stimulating factors. Efficacy has especially been seen when these cytokines have been used in combination with the more conventional antiviral agents. Due to the many biological functions exerted by cytokines and their interweaving of biological effects with other cytokines, they appear to have the potential to both inhibit as well as enhance viral infections, depending upon how they are used, and caution is therefore urged in their use.

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Immunomodulator Effects on the Friend Virus Infection in Genetically Defined Mice

Cited by 7 publications

References 23 publications

Effects of Type I Interferons on Friend Retrovirus Infection

Effects of Type I Interferons on Friend Retrovirus Infection

Imexon-Induced Apoptosis in Multiple Myeloma Tumor Cells Is Caspase-8 Dependent

Cyotkines as Potential Therapies for Human Immunodeficiency Virus Infections

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