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Immunological Effects of Ketoconazole, Itraconazole And Utah State University DigitalCommons@USU All Graduate Theses and Dissertations Graduate Studies 5-1990 Immunological Effects of Ketoconazole, Itraconazole and Fluconazole on Lymphocyte Cell Proliferation and Natural Killer Cell Activity in Immune-Normal, Cyclosporine-Compromised and Cyclophosphamide-Compromised Mouse Models Jeffrey Tullis Mitchell Utah State University Follow this and additional works at: https://digitalcommons.usu.edu/etd Part of the Biology Commons Recommended Citation Mitchell, Jeffrey Tullis, "Immunological Effects of Ketoconazole, Itraconazole and Fluconazole on Lymphocyte Cell Proliferation and Natural Killer Cell Activity in Immune-Normal, Cyclosporine- Compromised and Cyclophosphamide-Compromised Mouse Models" (1990). All Graduate Theses and Dissertations. 4666. https://digitalcommons.usu.edu/etd/4666 This Thesis is brought to you for free and open access by the Graduate Studies at DigitalCommons@USU. It has been accepted for inclusion in All Graduate Theses and Dissertations by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. 1.\1 ~ 1 UNO LOCICAL EFFECTS OF KETOCONr\ Z OLE. ITRACONAZOLE AND FLUCONAZOLE ON L Y1\ l PHOCYTE CELL PRO LI FERr\TIOt' AND <"A T U RAL KILLER CELL ACTI V ITY IN I 1\ I ~ I U ' E- NOR,\IAL CYCLOSPORI NE-COII-IPRO:\ IISED AND CYCLOPI-IOSP HAtvll DE-COM PRO~IISED MOUSE MODELS hv .klltcl Tullis i\litchcll A th ~:.i:-. suhmiu cJ in par!i ;d fulfil!m t.::nl nf th e n.:quirl.'ments for th e lkg r c~.: of II-lASTER O F SC IENCE in Biology Approved: UTAH STATE UNI VERS ITY Logan, Utah l99U AC KNOWLEDG EMEN TS I wo uld lik e to thank Dr. Andy And erson, chairman of my committ ee, for his support and advise Jnd Dr. Reed \Varren fo r serving as a member o f my commiuec ~ tnd for his help and suggesti ons in the immunological aspects of my research. I :1 \so wnuld lik e to thank Dr . Stan Allen for hi s e ncouragement to pursue a maste rs degree and fo r his financial support anJ advice in regards to my rcsc::t rch project. I would also lik e to thank Roger Burger for his help with the immunological assays and for the use of the lab and Jeff Siems and Mary Q uinn for their help. I would especiall y lik e to thank my wife, C~trmalc c, for all her support , encouragement and the sacrifices she m;ttk in order fo r me to continue my ed uca tion. .J effrey Tullis Mit che ll Ill TABLE OF CONTENTS ACKNOWLEDGEMENTS······································ ···································· ····· ··· ··································· ····· II LIST OF TABLES ........................................................................................................................... i1· LIST OF FIGURES ......................................... ..... .................. ........................................................ .. vii ABSTRACT .......... .. ............... ... .. ..................... .. ...... ...... ........ .. ..................... ............................................ 1iii INTRODUCTION .......................................................................................................................................... 1 REVIE\V OF LITERATURE ................................................................................................................ ... 2 Fun gal Infec ti ons and Hos t Immunit y ............................... .............................................................. 2 I mmunosuppressive Agents.. ............................................................................................. ..... 2 Cyclophosphamide .................................................................................................... ···· ··········" Cyclosporin e ........................................................................................................ ................... 3 Antifungal Agent s ............................................ ...................................................................... .. ........... :; Kc1oco na zo le . ............ ...................... ........................................... ........... .................................. ~ ltraconazole ................................................................................................... ....................... 7 Fluconazole... .............. .. ... .. ..................................... .. ..... ........................... .......... ;-{ Ampholc ricin B ..................................................................................................................~ Su mma ry .. ····················· ....................................... 12 MATERIA LS AND METHODS .. .. ... ......................................................... 1.1 T- and B-Lymphocyte Proliferat ion Assays .. ............................................................................... 1.1 Natural Kille r-Ce ll Studies.. ...... ......... .. 1~ Lvmphocyte- Viabilit y Assay.. ... ........ 13 RESULTS ... ······················ ······································· ........... ) (, Effects of Antifungal Agents o n Cell Proliferation.. .................... 1r1 Effects of Antifungal Agents on Natural Kill er-Cell Activity .................................................... 10 Effects of Antifungal Agents on Lymphocyte Viabi lity .................. .......................................... .... 21 DI SCUSSIO N .. .. ...... ........................................... .................... .... ?'-.) LITERATURE C ITED .. ................................................................ ................................. 20 APPENDIX .. ........................................................................ ~<) ]\" LIST OF TAI!LES l. Effect of ketoconazole, itraconazole and Ouconazolc concentration on viJbility of LPS-stimula1 ed lymphocytes. Va lues are shown as percent.:tgc of ,·iable cells in comparison with con trols ............................................................................. 22 Up1akc of3[H[-Ihymidine expressed as counls per minule for ketocona7ole al 0, I. 2. ~. 8 and 16!'g/ ml in immune-normal, cvc losporinc (CY) and cyclophosphamide (CP) immune-compromised nwdels--T cells .. ....................................... 30 J. Uptake of 3[ H J-thyrnidine expressed as counts per minute for ketoconilzolc al 0, 1, 2. ~ . 8 and 16 !'g/ ml in immune-normal. cvclosporine (CY) and cvclophosphamide (CP) immune-compromised models--B cells .......................................... 31 -1.. Upt.:~ k c of 3[ HJ-thymidine expressed as counts per minute for itraconazo lc a1 0, I, 2, ~. 8 and 16 l'g/ ml in immune-normal, cyclosporine (CY) and cyclophosphamide (CP) immune-compromised models--T cells.. .. ................... 32 5. Uptake of 3( HJ-thymi dinc ex pressed JS coun ts per minute for itraconazolc at 0. I. 2. ~. 8 and 16 .U.g/ ml in immune-normal. cyclosporin e (CY) and cyclophosphamide (CP) immune-compromised models--B cells .................. ............... ....... 33 h. Uptake of3[HJ-thymidine e.x pr cssL" d as cou nt s per minute for llucon.:~zolc at 0. I, 2. -t, 8 and 16 ,U.g / ml in immune-normal. cyclosporine (CY) and cyclophosphamide (CP) immune-compromised modcls--T cells ......................................... :-\~ 7. Uptake of3[HJ-thymidine expressed as counts per minute for flucona zole al 0, I, 2. ~ . 8 and 16 J.Lg / ml in im mune-norm al, cyclosporine (CY) and cyclophosphamide (CP) immune-compromised models--B cells ......................................... 35 8. Uplake of3[H[-Ihymidine expressed os couniS pe r minule for ketoconazole at 0, 1., 2, ~ . 8 and 16 ,U.g/ ml in an immune normal. cyclosporin e (CY) and cyclophosphamide (CP) immune-compromised modcls--T cells ....................................... 36 9. Up1ake of 3[H[-Ihymid ine expressed as cou nl s per minUi e for ke1oconazole al 0. 1, 2, ~ . 8 and 16!'g/ ml in an immune normal. cyclosporine (CY) and cvclophosphamide (CP) immune-compromised models--B cells ......................................... 37 10. Uptake of 3[H]-Ihymidine ex pressed as counls per minute for i1raconazole at 0, 1, 2, 4, 8 and 16!'g/ ml in an immune norm al, cyclosporine (CY) and cyclophosphamide (C P) immune-cc>mpromised models--T ce lls ......................................... 38 11. Uptake of 3(H]-rhymidine expressed ~s count s per minute for itraconazole al 0, I, 2, 4, 8 and 16!'g/ml in an immune normal, cvclmporine (CY) and cyclophosphamide (C P) immune-wm pmmised models--B cells ........................................ 39 12. Uptake of J[HJ-thymidine exprc~:-.cd as counts per minute for fluc onazole al 0, 1, 2, 4, 8 and 16!'g/ml in an immune normal, cyclosporin e (CY) and cyclophosphamide (C P) imm unc-wmpromised models--T ce lls ......................................... AO Table Pa g<.: 13. Uptake of 3[HJ-thym idine expressed as counts per minute for nuconazolc at 0, l. 2. .!, 8 and 16 t>g/ ml in an immune normal , cyclos porine (C Y) and cyclophosphamide (C P) immu ne-compromised models--8 ce ll s .......................................... .It 14. Uptake of 3[HJ-thymidine ex pressed as cou nt s per minute for ketoconazole at 0, l, 2. .!, 8 and l6t>g/ ml in immune-norm al, cyclosporine (CY) and cvclo ph os phamide (CP) immune-compromised models--T cells .......................................... -12 15. Uptake of 3[HJ-thvmidine expressed as co unts per minute for ketoconazole at 0, I, 2, 4, 8 and l6t>g/ ml in immune-norm al, cyclosporine (CY) and cyclo phosphamide (C P) immune-compromised models--8 ce ll s ........................................ A3 16. Uptake
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