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osu1148586277.pdf (894.51 KB)
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Stress-induced suppression of natural killer cell activity during influenza viral infection: The role of glucocorticoids and opioids
Author Info
Tseng, Raymond J.
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=osu1148586277
Abstract Details
Year and Degree
2006, Doctor of Philosophy, Ohio State University, Oral Biology.
Abstract
Activation of neuroendocrine responses by restraint stress (RST) suppresses natural killer cell (NK) activity during an experimental influenza A/PR8 viral infection. RST-induced activation of the HPA axis upregulates glucocorticoids (GC) and endogenous opioids which may be responsible for the observed suppression of NK activity. GC receptor antagonism modulates trafficking and splenic cellularity. However, the specific effects on NK activity remain unclear. Opioid receptor antagonism with naltrexone (NTX) abrogates RST-induced suppression of splenic NK cytotoxicity suggesting endogenous opioids modulate NK cytotoxicity. However, the specific subtype of opioid receptors involved remains unclear. These studies examined the effects of GC and specific opioid receptor subtype antagonism on splenic NK cellularity and cytotoxicity. Additionally, these studies examined whether the opioid signaling mechanism involved a direct effect on NK cells or a possible modulation in NK-stimulatory cytokine mRNA expression. C57BL/6 mice were treated daily with the GC receptor antagonist RU486, the opioid receptor antagonist NTX, or ì-, ä-, or ê-opioid receptor specific antagonists. Mice were infected intra-nasally with A/PR8 virus and underwent daily RST. Splenocytes were obtained three days post infection. For in vitro studies, splenocytes were incubated with NTX or morphine (MOR) and tested for cytolytic activity at 24 and 48 hours. NK cytotoxicity was assessed using a standard chromium release assay. FACS analysis was used to detect the number of CD3-DX5+ NK cells. Cytokine mRNA expression was assessed using realtime PCR. RST-induced suppression of NK activity was a result of decreases in number of splenic NK cells and cytotoxicity. GC Receptor antagonism restored cellularity and ì-opioid receptor antagonism restored NK cytolytic activity. Splenic NK cells incubated with morphine or NTX for up to 48 hours showed no change in NK cytotoxicity. Preliminary data suggested that antagonism of opioid receptors had no effect on splenic IFN-ã, IL-2, IL-12 or IL-15 mRNA expression in RST, infected mice. These findings suggest RST-induced GCs and ì-subtype endogenous opioids modulate NK cellularity and cytotoxicity, respectively, in pharmacologically-reversible manners. Further, opioid-induced modulation of cytotoxic activity does not occur via direct stimulation of NK cells, nor via the modulation of NK-stimulatory cytokine mRNA expression.
Committee
John Sheridan (Advisor)
Pages
141 p.
Keywords
influenza
;
stress
;
glucocorticoids
;
opioids
;
natural killer cells
;
NK
;
naltrexone
;
naloxone
;
cytokine
;
cytotoxicity
;
cellularity
;
lung
;
spleen
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Citations
Tseng, R. J. (2006).
Stress-induced suppression of natural killer cell activity during influenza viral infection: The role of glucocorticoids and opioids
[Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1148586277
APA Style (7th edition)
Tseng, Raymond.
Stress-induced suppression of natural killer cell activity during influenza viral infection: The role of glucocorticoids and opioids.
2006. Ohio State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=osu1148586277.
MLA Style (8th edition)
Tseng, Raymond. "Stress-induced suppression of natural killer cell activity during influenza viral infection: The role of glucocorticoids and opioids." Doctoral dissertation, Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1148586277
Chicago Manual of Style (17th edition)
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Document number:
osu1148586277
Download Count:
870
Copyright Info
© 2006, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.