Enhancement of Mice Susceptibility to Infection with Listeria monocytogenes by the Treatment of Morphine

Abstract

Abstract:The effect of morphine on the susceptibility of BALB/c mice to diarrheagenic Escherichia coli, Shigella flexneri, Listeria monocytogenes, Salmonella Enteritidis, Yersinia enterocolitica, was examined via the intraperitoneal inoculation. Morphine treatment increased the susceptibility to S. Enteritidis and L. monocytogenes, resulting in bacteremia and central nervous system (CNS) invasion (for L. monocytogenes), while the infection with other bacteria did not show the systemic dissemination in the morphinetreated mice. Notably, L. monocytogenes infection caused 100% mortality with a mean survival time (MST) of 1.3 days in morphine-treated mice, but untreated mice did not die. The present data suggested that individuals using heroin or treated with morphine derivatives might be at high risk for listeriosis, especially those who are immunocompromised. Recent increasing consumption of morphine may propose the necessity for further epidemiological surveillance on infectious diseases.

Opiate abuse, innate immunity, and bacterial infectious diseases

“…Experimental animal studies showed that opioid treatment causes increased susceptibility and mortality to various bacterial infections, including S. pneumoniae [87,88], K. pneumoniae [86], acute Toxoplasma gondii [11], oral Salmonella typhimurium [24], Candida albicans [81], Acinetobacter baumannii [40], S. aureus [38], and Listeria monocytogenes [2]. Although opiate addiction has been identified as a risk factor for clinical tuberculosis [17], an in vitro infection study, contrary to other bacterial infection studies, showed that morphine stimulated the phagocytosis of M. tuberculosis by human microglial cells, the resident macrophages of the brain.…”

The Effects of Opioids on Immune Cells, Functions and Diseases

“…In mice, chronic morphine has been shown to modulate bacterial killing by inhibition of NO release (Bhaskaran et al 2007;Menzebach et al 2004). Our laboratory's previous data and several other studies indicate that chronic morphine, by inhibition of NO release, increases susceptibility to bacterial infection, resulting in bacteremia and bacterial invasion of the CNS (Asakura et al 2006;Bhaskaran et al 2007;Wang et al 2005). A recent study by Singh and Singal (2007), notes that morphine administration has a dosedependent biphasic modulation in Leishmania donovani infected mice and peritoneal macrophages in vitro, via a NO-dependent mechanism.…”

Opioids and Infections in the Intensive Care Unit Should Clinicians and Patients be Concerned?

“…There is a substantial experimental literature documenting the immunosuppressive effects of opioids at the receptor (Beagles et al 2004;Tegeder and Geisslinger 2004) cell, (Hatsukari et al 2006), organ , and organism (Asakura et al 2006) level. Since infection is the most common consequence of immunosuppression, most studies have concentrated on one of three infectious models: (1) the effects of chronic opioid exposure on the severity or lethality of a new infectious or lipopolysaccharide (LPS) challenge (MacFarlane et al 2000;Ocasio et al 2004); (2) the effect of initiating opioid therapy in a previously infected animal (Chao et al 1990); or (3) the course of an infection induced in an animal previously made tolerant to opioids and then acutely withdrawn during the infection (Feng et al 2005).…”

“…Since infection is the most common consequence of immunosuppression, most studies have concentrated on one of three infectious models: (1) the effects of chronic opioid exposure on the severity or lethality of a new infectious or lipopolysaccharide (LPS) challenge (MacFarlane et al 2000;Ocasio et al 2004); (2) the effect of initiating opioid therapy in a previously infected animal (Chao et al 1990); or (3) the course of an infection induced in an animal previously made tolerant to opioids and then acutely withdrawn during the infection (Feng et al 2005). Generally, opioids have been found to have deleterious effects in all three infectious paradigms and across a broad range of pathogenic microorganisms: invasive intracellular (Asakura et al 2006), extracellular , and enteric bacteria, (Hilburger et al 1997), mycobacteria (Olin et al 2007), protozoans (Chao et al 1990), yeasts (Di Francesco et al 1997), and viruses (Hu et al 2005). Table 1 summarizes experimental animal studies that have reported mortality ( Table 1).…”

“…Morphine treatment for 14 days prior to infection with ongoing opioid administration or a single injection 14 or 21 days after infection 8 days after infection, the mortality rate was 100% in morphine-treated animals and zero for non-morphine animals Wang et al 2005 Streptococcus pneumoniae lung infection 24 h of opioid exposure followed by infection with ongoing opioid administration After 7 days, 87% of morphine-treated animals died versus 20% of animals not receiving morphine Feng et al 2005 Salmonella enterica, intraperitoneal Opioid withdrawal followed by infection Using virulent organisms, there was no difference in overall mortality but opioid-withdrawal animals had shorter time to death. Using attenuated organisms, withdrawal animals had 56% mortality compared to 11% in animals never exposed to morphine Asakura et al 2006 Listeria monocytogenes, intraperitoneal 24 h of opioid exposure followed by infection with ongoing opioid administration For Listeria, 100% mortality in morphine-treated animals versus 0% mortality in non-treated. No effect of morphine treatment for salmonella or E. coli infections multiple studies that reported that a single large morphine dose after an established infection was fatal compared to equivalent doses in noninfected animals is unclear.…”