Opioid use increases risk of infections

According to the Vanderbilt University Medical Center study, opioid users have a significantly increased risk of infections severe enough to require treatment at the hospital, such as pneumonia and meningitis, as compared to people who don't use opioids. People who use opioids have higher risk of invasive pneumococcal diseases.

Invasive pneumococcal diseases are serious infections caused by the Streptococcus pneumoniae bacteria, with mortality ranging from 5 percent to 20 percent. These invasive diseases include a range of illnesses such as meningitis, bacteremia and invasive pneumonia.

The association between opioid use and the risk of invasive pneumococcal diseases was strongest for opioids used at high doses, those classified as high potency and long-acting, which would be the extended release or controlled release formulations," said lead author Andrew Wiese, PhD, MPH, postdoctoral research fellow in the Department of Health Policy at Vanderbilt University School of Medicine.

Opioids previously described as immunosuppressive in prior experimental studies conducted in animals, had the strongest association with invasive pneumococcal diseases in humans, measuring daily prescription opioid exposure for each study individual and combined that information with Active Bacterial Core (ABC) surveillance system data, which is a VUMC laboratory and population-based surveillance system conducted in partnership with the Tennessee Department of Health and the CDC Centers for Disease Control and Prevention to monitor invasive infectious diseases in Tennessee.

The increase in opioid use has led to an increased interest towards well-known and also previously under- recognized adverse effects associated with opioid use. Previous studies conducted in animal models had demonstrated that certain opioids can cause immunosuppression and render experimental animals susceptible to infections. However, the clinical implications of those observations in humans were unclear.
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Targeted cell metabolism can improve immune system

Immune system can become so over-activated when fighting infections that the resulting inflammatory response can lead to death. Excessive response by the immune system can be modulated by targeted manipulation of the sugar metabolism to produce an immune response that eliminates the pathogens without causing any harmful to the immune system.

Using 2-Deoxy-D-glucose 2-DG during the infection make this possible, adding 2-DG, that prevents glycolysis, causes increased production of interleukin-12 IL-12, a pro-inflammatory cytokine, while suppressing the production of interleukin-10, an anti-inflammatory cytokine.

IL-12 triggers a specific T-cell immune response, which is part of the cellular immune response, to specifically boost the defence mechanisms that serve to eliminate intracellular pathogens like listeria. Addition of 2-DG changes the nature of the immune response and the intensity of the inflammatory process, inflammation is controlled so that the immune system is able to manage the situation without allowing the infection to leads to a deadly outcome.

This prevents excessive inflammatory responses, following addition of of 2-DG, only p40 is upregulated, while no p35 is produced. This modified cytokine profile, there is also a simultaneous increase in IL-23 expression which could subsequently bring about modified recruitment of immune cells and hence have a decisive influence on the intensity of the immune response.

The metabolic increased production of activating mediators with simultaneous inhibition of immunosuppressive mediators. Manipulation of the sugar metabolism and associated modulation of the immune system could open up new options for treating specific infectious and autoimmune diseases
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