Effect of murine retrovirus infection and aging on the immune defenses against to coxsackieviruses and Cryptosporidium parvum
AdvisorWatson, Ronald R.
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PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractAcquired immune deficiency syndrome (AIDS) and aging are associated with significant immune dysfunction and increased oxidative stress, resulting in increased susceptibility to opportunistic infections, cancers, autoimmune diseases, and death. Human immunodeficiency virus (HIV) infection and aging lower host defenses by modulating cytokine production to alter T and B cell functions. The overall objective of this study is to determine effect of Murine AIDS (MAIDS), its cofactors and aging on opportunistic infection, and the potential of immunomodulation roles of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) on ameliorating the immunological abnormality caused by retrovirus infection and aging. DHEA(S) was previously shown to have immune enhancing properties during (MAIDS) and the aging. DHEA(S) significantly increased T-cell proliferation, restored secretion of Th1 cytokines production, and normalized secretion of Th2 cytokine. Survival was significantly increased in the 29-month-old mice treated by DHEA. DHEAS plus antioxidants significantly normalized immune function, as well as maintained hepatic vitamin E levels nearer control. In addition, DHEAS supplementation increased resistance to cryptosporidiosis in aged mice. Our study suggests that DHEA(S) alone and especially DHEAS plus antioxidant nutrients can prevent immune dysfunction in aging as well as aging, retrovirus infected mice. Chronic ethanol (EtOH) consumption causes immune dysfunction and further exacerbates immune dysfunction and cytokine imbalance during MAIDS. DHEAS supplementation during MAIDS with EtOH consumption partially restored immune function, prevented the further dysregulation of cytokines and hepatic lipid peroxidation, and maintained hepatic vitamin E levels to near normal levels. Coxsackievirus B3 (CVB3) initiates myocarditis especially in the immunologically deficient. EtOH or cocaine as a cofactor may exacerbates CVB3 cardiomyopathy in AIDS patients. In our study, the resistant mouse strain to CVB3 become susceptible due to the immune dysfunction in MAIDS. EtOH consumption or cocaine injection during MAIDS greatly exacerbated the pathogenesis of CVB3 infection and showed significant heart lesions. Our data suggest that EtOH consumption or cocaine injection shifted the cytokine balance in favor of a Th2 response, by enhancing Th2 cytokine and/or by suppressing Th1 cytokine function. MAIDS facilitated severe cardiotoxicity during CVB3 infection, MAIDS with EtOH consumption or cocaine injection was more susceptible to cardiotoxicity of CVB3 than the retrovirus infection alone.
Degree ProgramGraduate College