The immunomodulatory properties of AZT used in the treatment of AIDS

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dc.contributor.authorMcKallip, Robert Jamesen
dc.contributor.departmentBiologyen
dc.date.accessioned2014-03-14T21:37:25Zen
dc.date.adate2009-06-10en
dc.date.available2014-03-14T21:37:25Zen
dc.date.issued1994en
dc.date.rdate2009-06-10en
dc.date.sdate2009-06-10en
dc.description.abstractAZT (3'-azido-2’, 3’-dideoxythymidine) has been shown to prolong the survival of patients infected with human immunodeficiency virus (HIV) and decrease the severity of opportunistic infections. Such studies have prompted the use of AZT to treat symptomless individuals infected with HIV in the hope of delaying or even preventing the progression to acquired immunodeficiency syndrome (AIDS). However, before chronic use of AZT in symptomless individuals is initiated, it is important to establish whether this anti-viral drug would directly alter the phenotype and functions of the cells involved in the immune system. In the current study, we observed that AZT when administered orally for 7 -14 days into DBA/2 mice at 500 - 1000 mg/kg body weight induced a dose-dependent decrease in cellularity of the thymus. AZT caused significant alterations in the thymus resulting from a significant decrease in the number of double-positive (CD4⁺CD8​​⁺) cells and an increase in the number of double-negative (CD4⁻CD8⁻) cells. Interestingly, after the i.p. administration of interleukin-2 (IL-2) simultaneously with AZT, the total cellularity of the thymus was completely reconstituted. We also observed that AZT effectively suppressed the in vivo T cell response to conaibumin and gp120 of HIV. Furthermore, the addition of AZT to in vitro cultures caused a dose-dependent decrease in T and B cell proliferative responses to mitogens at 50μM or greater concentrations. Also, AZT inhibited the generation of cytotoxic T lymphocytes when added to the culture and this inhibition was reconstituted by the addition of exogenous IL-2. Together, our studies demonstrate that AZT modulates the phenotype and function of cells of the immune system which, in turn, could have marked repercussions on immune responses of the host toward infections and cancers. Also, our data demonstrating that AZT can suppress T cell responsiveness against HIV antigens caution against chronic use of AZT in asymptomatic HIV-infected individuals.en
dc.description.degreeMaster of Scienceen
dc.format.extentx, 86 leavesen
dc.format.mediumBTDen
dc.format.mimetypeapplication/pdfen
dc.identifier.otheretd-06102009-063223en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-06102009-063223/en
dc.identifier.urihttp://hdl.handle.net/10919/42995en
dc.language.isoenen
dc.publisherVirginia Techen
dc.relation.haspartLD5655.V855_1994.M352.pdfen
dc.relation.isformatofOCLC# 30351766en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject.lccLD5655.V855 1994.M352en
dc.subject.lcshAIDS (Disease) -- Treatmenten
dc.subject.lcshAZT (Drug)en
dc.titleThe immunomodulatory properties of AZT used in the treatment of AIDSen
dc.typeThesisen
dc.type.dcmitypeTexten
thesis.degree.disciplineBiologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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