The Effects of Morphine Withdrawal on Immune Functioning

The Effects of Morphine Withdrawal on Immune Functioning

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It is clear from research that has been performed over the past several years that both stress and morphine results in immune dysfunction. However, in contrast there are very few studies that have examined the role that morphine withdrawal plays in causing decrements to immune functioning. Examining if and how morphine withdrawal brings about dysfunction is a worthwhile endeavor for several reasons. First, drug abusers do not experience episodes of a qhighq at all times, but go through periods of drug withdrawal, and given the huge coincidence between drug abuse and infection examining these processes may help to alleviate this problem. Secondly, post-surgical patients are given morphine and also experience periods of withdrawal in hospital settings where they are prone to contract an infection, resulting in severe post-surgical complications. Therefore, it was the goal of this research to examine the means by which morphine withdrawal may effect immune functioning and to investigate the underlying mechanisms that contribute to the observed dysfunctions. To this end, the first set of studies examined the role of morphine withdrawal in T helper cell differentiation, and it was demonstrated that withdrawal contributes to polarization by biasing cells toward the Th2 lineage. Furthermore, it was demonstrated that withdrawal may be blunting the production of IL-12, and it was observed that both the mu-opioid receptor and corticosterone may be involved in this decreased response. Decreased IL-12 production may result in a default in the development of T helper cells down the Th2 pathway. Given this hypothesis, the means by which morphine withdrawal regulates IL-12 production was explored. This set of studies demonstrated that morphine withdrawal may be increasing cyclic adenosine monophosphate (cAMP) which activates protein kinase A (PKA). PKA activation then (via an unknown mechanism) decreases phosphorylation of IkappaB preventing its degradation and the release of NF-kappaB, which subsequently decreases IL-12 production by hindering transactivation of the IL-12 p40 gene by NF-kappaB. Finally, these series of studies have extended our knowledge in an underrepresented field of study, however many questions still remain and it is crucial to investigate the answers given the wide use of morphine.TGF-pi and IL-10 (23). Our lab has demonstrated that low dose morphine treatment of lymph node derived T lymphocytes results in impaired Con A induced proliferation and IL-2 and EFN-y production, this decrement was accompanied by ananbsp;...

Title:The Effects of Morphine Withdrawal on Immune Functioning
Author:Jennifer Kelschenbach
Publisher:ProQuest - 2006


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