Opiate abuse, innate immunity, and bacterial infectious diseases

Abstract

The first line of defense against invading bacteria is provided by the innate immune system. Morphine and other opiates can immediately disrupt the body's first line of defense against harmful external bacteria. Opiate, for example morphine, abuse degrades physical and physiologic barriers, and modulates phagocytic cells (macrophages, neutrophils) and, nonspecific cytotoxic T cells (gammadelta T), natural killer cells, and dendritic cells, that are functionally important for carrying out a rapid immune reaction to invading pathogens. In vitro studies with innate immune cells from experimental animals and humans and in vivo studies with animal models have shown that opiate abuse impairs innate immunity and is responsible for increased susceptibility to bacterial infection. However, to better understand the complex interactions between opiates, innate immunity, and bacterial infection and develop novel approaches to treat and even prevent bacterial infection in the opiate-abuse population, there is an urgent need to fill the numerous gaps in our understanding of the cellular and molecular mechanisms by which opiate abuse increases susceptibility to bacterial infection.

Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

“…Indeed, morphine and its derivatives interact with the mu receptor expressed on various immune cell types including lymphocytes and NK cells. Multiple in vitro and in vivo experiments have demonstrated that it can suppress production of cytokines and proliferation of lymphocytes and inhibit NK cell activity in humans, monkey and rodents [39][40][41]. Drug abuse in our cohort of HCV-exposed IDUs could account for low IFN-γ production during baseline.…”

“…This probably reflects a shut-off mechanism to guard against liver inflammation and the development of immune suppressive IL-10 NK cells. Alternatively, it was demonstrated that HCV infected hepatocytes express enhanced levels of HLA-E and that the HLA-A2 restricted epitope HCV core AA (35)(36)(37)(38)(39)(40)(41)(42)(43)(44) stabilizes HLA-E expression [18]. Since NKG2A binds to HLA-E, enhanced expression of NKG2A by NK cells from chronic HCV patients resulted in reduced cytolysis of HLA-E expressing hepatocytes [18].…”

Morphine Disrupts Interleukin-23 (IL-23)/IL-17-Mediated Pulmonary Mucosal Host Defense against Streptococcus pneumoniae Infection

“…Previous studies have shown that opiate abuse causes immunosuppression by disrupting both innate and adaptive components of the immune system (26,33). Opiate abuse is a critical risk factor for increasing susceptibility and severity of bacterial infection, including S. pneumoniae (31,32).…”

Depletion and recovery of lymphoid subsets following morphine administration

“…Opioid use and abuse renders individuals susceptible to infection (see Eisenstein et al, 2006;Wang et al, 2008) and a variety of mechanisms have been proposed to explain how opioids suppress the immune system. These mechanisms include effects on both the innate and adaptive branches of the immune system.…”