Increased Sensitivity to<i>Salmonella enterica</i>Serovar Typhimurium Infection in Mice Undergoing Withdrawal from Morphine Is Associated with Suppression of Interleukin-12

Feng, Ping; Wilson, Qiana M.; Meissler, Joseph J.; Adler, Martin W.; Eisenstein, Toby K.

doi:10.1128/iai.73.12.7953-7959.2005

Cited by 29 publications

(25 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, cats infected with feline immunodeficiency virus given morphine chronically and then withdrawn had no alteration in their levels of feline immunodeficiency virus (4). The third paper is from our laboratory and showed that mice withdrawn from morphine are sensitized to systemic (intraperitoneal) infection with Salmonella (17). The present results expand this limited data to test the effect of withdrawal on an oral bacterial infection.…”

Section: Discussionsupporting

confidence: 57%

“…This time point was chosen because it coincides with the onset of maximal systemic immunosuppression (31). When the results are compared, withdrawal from morphine produces less robust effects on oral Salmonella infection (present study) than on intraperitoneal Salmonella infection, the subject of a previous paper from our laboratory (17). The effects of withdrawal on oral Salmonella infection are also several orders of magnitude less robust than those observed when Salmonella is given orally coincident with initiation of morphine administration (25).…”

Section: Discussionmentioning

confidence: 57%

“…Further, we also tested the resistance of mice in withdrawal to an intraperitoneal (i.p.) infection with live, virulent Salmonella enterica serovar Typhimurium and found that abstinence increased their susceptibility (17). We hypothesized that withdrawal might lead to a condition of underlying sepsis (16), where sepsis is defined here narrowly as the presence in the blood, peritoneal fluid, tissues, or organs of bacteria normally confined to the gastrointestinal tract.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Morphine Withdrawal Lowers Host Defense to Enteric Bacteria: Spontaneous Sepsis and Increased Sensitivity to Oral Salmonella enterica Serovar Typhimurium Infection

Feng¹,

Truant²,

Meissler³

et al. 2006

Infect Immun

Self Cite

View full text Add to dashboard Cite

Understanding the consequences of drug withdrawal on immune function and host defense to infection is important. We, and others, previously demonstrated that morphine withdrawal results in immunosuppression and sensitizes to lipopolysaccharide-induced septic shock. In the present study, the effect of morphine withdrawal on spontaneous sepsis and on oral infection with Salmonella enterica serovar Typhimurium was examined. Mice were chronically exposed to morphine for 96 h by implantation of a slow-release morphine pellet. Abrupt withdrawal was induced by removal of the pellet. In the sepsis model, bacterial colonization was examined and bacterial species were identified by necropsy of various tissues. It was found that at 48 h postwithdrawal, morphine-treated mice had enteric bacteria that were detected in the Peyer's patches (4/5), mesenteric lymph nodes (4/5), spleens (4/10), livers (6/10), and peritoneal cavities (8/10). In placebo pelletwithdrawn mice, only 2/40 cultures were positive. The most frequently detected organisms in tissues of morphine-withdrawn mice were Enterococcus faecium followed by Klebsiella pneumoniae. Both organisms are part of the normal gastrointestinal flora. In the infection model, mice were orally inoculated with S. enterica 24 h post-initiation of abrupt withdrawal from morphine. Withdrawal significantly decreased the mean survival time and significantly increased the Salmonella burden in various tissues of infected mice compared to placebo-withdrawn animals. Elevated levels of the proinflammatory cytokines were observed in spleens of morphine-withdrawn mice, compared to placebo-withdrawn mice. These findings demonstrate that morphine withdrawal sensitizes to oral infection with a bacterial pathogen and predisposes mice to bacterial sepsis.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 57%

mentioning

confidence: 99%

See 1 more Smart Citation

Morphine Withdrawal Lowers Host Defense to Enteric Bacteria: Spontaneous Sepsis and Increased Sensitivity to Oral Salmonella enterica Serovar Typhimurium Infection

Feng¹,

Truant²,

Meissler³

et al. 2006

Infect Immun

Self Cite

View full text Add to dashboard Cite

show abstract

“…18 The clinical relevance of these effects is unknown and there are no recommendations for the use of opioids in various clinical situations regarding the immunological consequences of these drugs. Animal studies suggest that opiates withdrawal induces a state of immunosuppression that would increase the risk of infections 19 and, thus, changes in immunomodulation caused by certain drugs may be responsible for a part of the HAI-related complications in critical medicine. Recently, it was reported that anesthetic techniques and different sedoanalgesia regimens could be an important confounding factor when comparing sepsis mortality investigations.…”

Section: Introductionmentioning

confidence: 99%

Opioids and immunosupression in oncological postoperative patients

Bonilla-García

Cortiñas-Sáenz

Pozo-Gavilán

2017

Rev. Assoc. Med. Bras.

View full text Add to dashboard Cite

“…Morphine withdrawal can be induced either by simple cessation of morphine (abrupt withdrawal) (3) or by cessation of morphine with administration of morphine antagonists (precipitated withdrawal) (4). Elegant studies from the Eisenstein laboratory (3,(5)(6)(7)(8)(9)(10) were the first to demonstrate that both abrupt and precipitated morphine withdrawal result in significant immunosuppression with significant changes in several key cytokines, including IL-12p40.…”

mentioning

confidence: 99%

Morphine Withdrawal Stress Modulates Lipopolysaccharide-induced Interleukin 12 p40 (IL-12p40) Expression by Activating Extracellular Signal-regulated Kinase 1/2, Which Is Further Potentiated by Glucocorticoids

Das

Kelschenbach

Charboneau

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Withdrawal stress is a common occurrence in opioid users, yet very few studies have examined the effects of morphine withdrawal (MW) on immune functioning or the role of glucocorticoids in MW-induced immunomodulation. This study investigated for the first time the role of glucocorticoids in MW modulation of LPS-induced IL-12p40, a key cytokine playing a pivotal role in immunoprotection. Using WT and -opioid receptor knock-out mice, we show that MW in vivo significantly attenuated LPS-induced IL-12p40 mRNA and protein expression. The role of glucocorticoids in MW modulation of IL-12p40 was investigated using a murine macrophage cell line, CRL2019, in an in vitro MW model. Interestingly, MW alone in the absence of glucocorticoids resulted in a significant reduction in IL-12p40 promoter activity and mRNA and protein expression. EMSA revealed a concurrent decrease in consensus binding to transcription factors NFB, Activator Protein-1, and CCAAT/enhancer-binding protein and Western blot analysis demonstrated a significant activation of LPSinduced ERK1/2 phosphorylation. Interestingly, although glucocorticoid treatment alone also modulated these transcription factors and ERK1/2 activation, the addition of glucocorticoids to MW samples resulted in a greater than additive reduction in the transcription factors and significant hyperactivation of LPS-induced ERK1/2 phosphorylation. ERK inhibitors reversed MW and MW plus corticosterone inhibition of LPS-induced IL-12p40. The potentiating effects of glucocorticoids were non-genomic because nuclear translocation of glucocorticoid receptor was not significantly different between MW and corticosterone treatment. This study demonstrates for the first time that MW and glucocorticoids independently modulate IL-12p40 production through a mechanism involving ERK1/2 hyperactivation and that glucocorticoids can significantly augment MW-induced inhibition of IL-12p40.Drugs of abuse have long been known to contribute to immunosuppression (1) affecting both innate and adaptive immunity in experimental animals as well as in humans (2). Although a wealth of data exists on the effects of morphine treatment on immune function, very few studies have investigated the effects of morphine withdrawal on immune parameters, and of these even fewer describe the underlying mechanisms that modulate morphine withdrawal-induced immunosuppression. Morphine withdrawal can be induced either by simple cessation of morphine (abrupt withdrawal) (3) or by cessation of morphine with administration of morphine antagonists (precipitated withdrawal) (4). Elegant studies from the Eisenstein laboratory (3,(5)(6)(7)(8)(9)(10) were the first to demonstrate that both abrupt and precipitated morphine withdrawal result in significant immunosuppression with significant changes in several key cytokines, including IL-12p40.Stress has been shown to play a major role in several aspects of morphine use and abuse. These roles include precipitating abuse, enhancing drug seeking (11), potentiating responses to other stressors, a...

show abstract

Increased Sensitivity toSalmonella entericaSerovar Typhimurium Infection in Mice Undergoing Withdrawal from Morphine Is Associated with Suppression of Interleukin-12

Cited by 29 publications

References 41 publications

Morphine Withdrawal Lowers Host Defense to Enteric Bacteria: Spontaneous Sepsis and Increased Sensitivity to Oral Salmonella enterica Serovar Typhimurium Infection

Morphine Withdrawal Lowers Host Defense to Enteric Bacteria: Spontaneous Sepsis and Increased Sensitivity to Oral Salmonella enterica Serovar Typhimurium Infection

Opioids and immunosupression in oncological postoperative patients

Morphine Withdrawal Stress Modulates Lipopolysaccharide-induced Interleukin 12 p40 (IL-12p40) Expression by Activating Extracellular Signal-regulated Kinase 1/2, Which Is Further Potentiated by Glucocorticoids

Contact Info

Product

Resources

About