Anesthetics decrease lung injury severity in mice


Streptococcus pneumoniae, a bacterium that can induce pneumococcal pneumonia, has for long been the scourge of post-influenza patients. As one of the major pathogens responsible for secondary bacterial pneumonia, S. pneumoniae, even in this modern age of antibiotics, continues to pose a significant threat to patients weakened by influenza.

Although there are therapies that target the life cycles of pathogens, there is a need for remedies that affect the patient’s immune system, according to the authors of a report published in the September 2015 issue of the journal Anesthesiology.

The researchers discussed one of these potential rememdies through a study that showed certain anesthetic drugs can inhibit the bacterial infections that patients develop after suffering from the flu.

The research teams hailed from the Johns Hopkins School of Medicine and the University of Buffalo School of Medicine and were led respectively by Krishnan Chakravarthy, resident physician in the department of anesthesiology and critical care medicine, and Paul Knight, professor of anesthesiology.

While inhaled anesthetics, such as nitrous oxide and halothane, have been used during surgery for decades, the mechanisms by which the drugs produce anesthetic and immunoprotective effects have yet to be completely understood. In this new study, halothane is shown to decrease the extent of lung injury caused by S. pneumoniae in post-flu mice.

At the beginning of the study, mice were infected with the H1N1 viral strain, after which they were exposed to halothane. Four days after the viral infection, the mice were again anesthetized with halothane.

To track symptoms caused by the flu and the later bacterial introduction, which occurred six days after the flu infection, the researchers first monitored the mice for weight loss during the post-viral infection period. On day seven, a more comprehensive evaluation of the mice’s symptoms was conducted, examining for additional signs of illness such as hunched posture, labored breathing, impaired gait and lethargy.

Upon surveying the results, the investigators noted that the anesthetized mice showed significantly reduced clinical symptoms on days six and seven, when the rodents were examined for indications of flu and secondary bacterial pneumonia.

In comparison with the non-anesthetized control group, the mice that had been exposed to halothane had airway albumin levels that were four times lower, meaning that their lungs were less damaged. Moreover, evaluation of the bacterial population on day seven revealed that the anesthetized rodents had nearly 450-fold less bacteria than the control group.

The researchers, however, concluded that halothane exposure on its own does not improve the animals’ immune function. For the animals that were flu-free but received halothane anyway, the treatment did not enhance their baseline immune system.

To clarify how halothane regulated the mouse immune system, the researchers next studied the effects of halothane on different aspects of the immune system.

Among the groups of mice, non-anesthetized rodents that had been exposed to both the flu and secondary bacterial pneumonia had the highest number of macrophages. This group nevertheless proved to be the least capable of producing an adequate antibacterial response. Halothane mitigated this impairment of macrophage antibacterial function, improving the animals’ outcomes.

The researchers also inferred that halothane augmented the rodents’ immune system response by monitoring the effects of type I and type II interferons, proteins that under normal host conditions function to minimize viral infection. Six days after being infected with the flu, the mice were examined for variations in type I and type II interferon expression. While type I interferon levels were low for both anesthetized and non-anesthetized mice, type II interferon expression was higher in the non-anesthetized mice.

Halothane appeared to have reduced type II interferon expression in the anesthetized mice to almost undetectable levels.

The impaired antibacterial response of the non-anesthetized rodents, combined with their increased type II interferon levels, led the researchers to posit that halothane enables a sufficient antibacterial response by minimizing the production of type II interferons.

After observing the way halothane regulates the immune system, the researchers say that it and other similar anesthetics could become the basis for new therapies.

Because there’s always a concern that bacteria will become resistant to treatments, researchers work to find remedies like this one that modulate the immune system response instead of engaging with a specific pathogen (which could eventually lead to resistance).

Furthermore, by maintaining the capacity of the host’s immune system, anesthetics would help to fend off secondary infections such as secondary bacterial pneumonia in the wake of new and virulent influenza strains.

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