Opioid Drug Abuse and Modulation of Immune Function: Consequences in the Susceptibility to Opportunistic Infections

Abstract

Infection rate among intravenous drug users (IDU) is higher than the general public, and is the major cause of morbidity and hospitalization in the IDU population. Epidemiologic studies provide data on increased prevalence of opportunistic bacterial infections such as TB and pneumonia, and viral infections such as HIV-1 and hepatitis in the IDU population. An important component in the intravenous drug abuse population and in patients receiving medically indicated chronic opioid treatment is opioid withdrawal. Data on bacterial virulence in the context of opioid withdrawal suggest that mice undergoing withdrawal had shortened survival and increased bacterial load in response to Salmonella infection. As the body of evidence in support of opioid dependency and its immunosuppressive effects is growing, it is imperative to understand the mechanisms by which opioids exert these effects and identify the populations at risk that would benefit the most from the interventions to counteract opioid immunosuppressive effects. Thus, it is important to refine the existing animal model to closely match human conditions and to cross-validate these findings through carefully controlled human studies. Better understanding of the mechanisms will facilitate the search for new therapeutic modalities to counteract adverse effects including increased infection rates. This review will summarize the effects of morphine on innate and adaptive immunity, identify the role of the mu opioid receptor in these functions and the signal transduction activated in the process. The role of opioid withdrawal in immunosuppression and the clinical relevance of these findings will also be discussed.

Receipt of Opioid Analgesics by HIV-Infected and Uninfected Patients

“…26,47 Similarly, some evidence suggests that opioids may adversely impact the immune system. 18 Our univariate analysis demonstrated a trend towards lower CD4 cell counts among patients on opioids, a finding that may be confounded by indication and did not persist in multivariable analyses. Prior studies are inconsistent in their findings about the association between receipt of opioids and HIV biomarkers.…”

“…7,12,14 Whether in vitro effects of opioids on the immune system translate into clinical phenomena warrants further investigation. 18 The potential for medication interactions with antiretroviral agents also requires consideration when considering some opioid analgesics, particularly methadone. 22 In our sample, almost 5 % of the HIV-infected patients received methadone (data not otherwise shown).…”

“…[12][13][14][15] The benefits of opioids for treating painful conditions, such as neuropathy and osteonecrosis, which may occur more commonly among HIV-infected patients, must be balanced against 16,17 the possibility of increased risk for harm. Opioids may impact immune function, 18 be associated with toxicities [19][20][21] and interact with antiretrovirals. 22 There are limited recent data examining factors associated with opioid prescribing to HIV-infected patients.…”

Effects of flurbiprofen axetil on postoperative serum IL-2 and IL-6 levels in patients with colorectal cancer

“…Generally, patients should be awoken immediately after surgery, but some patients suffer from brain disorder, such confusion, hypersomnia, and restlessness. Although restlessness is transient, it leads to severe complications, such as accidental injury (Atkins, 2002;Roy et al, 2011). Morphine and tramadol are widely used to prevent postoperative restlessness in clinical application.…”

Evaluation of the alum–naloxone adjuvant activity against experimental murine leishmaniasis due to L. major

“…The activation of Th1 responses is associated with the production of cytokines such as IFN-c and IL-12 which stimulate the microbicidal activity of macrophages (Ameen 2010). Exposure to opioids increases the susceptibility to bacterial, fungal, and opportunistic infections (Friedman et al 2003;Roy et al 2011). It is now clear that the endogenous opioids modulate both innate and acquired immune responses (McCarthy et al 2001).…”