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Mechanisms of immunosuppression foll...

Rahim, Rahil Tamara Camille.

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Mechanisms of immunosuppression following administration of opioids and induction of abstinence.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Mechanisms of immunosuppression following administration of opioids and induction of abstinence./
作者:	Rahim, Rahil Tamara Camille.
面頁冊數:	200 p.
附註:	Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1237.
Contained By:	Dissertation Abstracts International65-03B.
標題:	Health Sciences, Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3125550
ISBN:	0496728393

Mechanisms of immunosuppression following administration of opioids and induction of abstinence.
Rahim, Rahil Tamara Camille.

Mechanisms of immunosuppression following administration of opioids and induction of abstinence. - 200 p.

Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1237.

Thesis (Ph.D.)--Temple University, 2004.

This thesis examines the immunomodulatory effects of opioids in vivo by studies on (1) the immunosuppressive effects of mu, kappa, and delta opioids administered via osmotic minipumps and (2) the mechanisms mediating immunosuppression following withdrawal from morphine. Our laboratory has shown that mice given morphine by s.c. implanted slow-release pellets for 48 hours have suppressed antibody responses to sheep red blood cells using a plaque-forming cell (PFC) assay. In the present studies, we investigated the immunomodulatory effects of morphine and other opioids in vivo using AlzetRTM osmotic minipumps. All opioids were immunosuppressive, with biphasic dose-response curves exhibiting maximal (approximately 50%) suppression of the PFC response at doses of 0.5 to 2 mg/kg/day 48 hours after pump implantation. We conclude that immunosuppression induced in vivo by opioid agonists is mediated not only via mu, but also via kappa and delta 2 opioid receptors.

ISBN: 0496728393Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Mechanisms of immunosuppression following administration of opioids and induction of abstinence.
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245 1 0 $a Mechanisms of immunosuppression following administration of opioids and induction of abstinence.
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500 $a Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1237.
500 $a Chair: Toby K. Eisenstein.
502 $a Thesis (Ph.D.)--Temple University, 2004.
520 $a This thesis examines the immunomodulatory effects of opioids in vivo by studies on (1) the immunosuppressive effects of mu, kappa, and delta opioids administered via osmotic minipumps and (2) the mechanisms mediating immunosuppression following withdrawal from morphine. Our laboratory has shown that mice given morphine by s.c. implanted slow-release pellets for 48 hours have suppressed antibody responses to sheep red blood cells using a plaque-forming cell (PFC) assay. In the present studies, we investigated the immunomodulatory effects of morphine and other opioids in vivo using AlzetRTM osmotic minipumps. All opioids were immunosuppressive, with biphasic dose-response curves exhibiting maximal (approximately 50%) suppression of the PFC response at doses of 0.5 to 2 mg/kg/day 48 hours after pump implantation. We conclude that immunosuppression induced in vivo by opioid agonists is mediated not only via mu, but also via kappa and delta 2 opioid receptors.
520 $a Following implantation of a morphine pellet, maximal immunosuppression was observed at 48 hours, with a return to normal levels by 96 hours. At 96 hours post pellet implantation, we examined the effect of withdrawal from morphine on the PFC response. Withdrawal was induced by two methods: (1) Precipitated withdrawal (PW): morphine pellets were removed and mice were given either a s.c. injection of naloxone (1 mg/kg) or implanted s.c. with a naloxone osmotic minipump (1 mg/kg/day). (2) Abrupt withdrawal (AW): morphine pellets were removed. Both AW and PW led to greater than 80% suppression in the PFC assay 24 hours post-withdrawal as compared with placebo-pelleted mice. Further studies were done at this time point to assess the mechanisms of immunosuppression. The results show that addition of highly purified normal macrophages, to cells from withdrawn mice, restored immune responses for both paradigms. Further, if highly enriched macrophages or B-cells from AW mice were added to cultures of normal unfractionated spleen cells, co-cultures were suppressed. These data suggest that morphine-withdrawal causes (1) a deficit in macrophage function and/or (2) active suppression by macrophages and B-cells. These studies raise the possibility that addicts undergoing episodes of withdrawal may experience immunosuppression that could provide periods of enhanced sensitization to infection.
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