Anesthetics' Impact on Inflammation Resolution
Although it once was believed that resolution of inflammation was a passive process, research done in the lab of Charles N. Serhan, PhD, uncovered that inflammation resolution is actually an active process. Controlling, stopping and reversing inflammation is a two-part function that involves inhibiting the pro-inflammatory process and promoting the pro-resolution process. Classic anti-inflammatories inhibit pro-inflammatory pathways and sometimes can delay pro-resolution pathways. Identifying and utilizing pro-resolution systems could serve to better control chronic inflammatory diseases or even give doctors a way to shift the body back into a state of balance.
What Problem Was Studied?
Certain agents given as anti-inflammatories have been shown to inhibit not only pro-inflammatory mediators, but pro-resolution mediators as well. These medications can relieve the inflammation, but they can’t tell the body to “go back to normal.”
Peritonitis: inflammation of the peritoneum (the membrane that lines part of the abdominal cavity)
Exudate: any fluid that filters from the circulatory system into areas of inflammation. Pus is an example of exudate found in infected wounds. Clear blister fluid is an example of an exudate that contains water together with some plasma proteins, but not many blood cells.
As part of their quest to understand the resolution of acute inflammation and understand the effects of different medications in resolution of inflammation, a research team from Brigham and Women’s Hospital and Harvard Medical School in Boston – led by Serhan and including Arthritis Foundation-funded scientist Kie Kasuga, PhD -- decided to look at one common source of acute inflammation: surgery. They wanted to determine whether drugs used during surgery had any effect on the resolution of inflammation brought about by surgery.
What Was Done in the Study?
Two commonly used surgical anesthetics were tested -- the topical medicine lidocaine and the inhaled medicine isoflurane. Rather than actually performing surgery, mice were injected with a substance to induce the acute inflammatory disease peritonitis. The mice were administered either lidocaine or isoflurane before or at the same time as the stimulus injection. The resolution of inflammation was then monitored over time.
Additional cellular-level experiments were conducted using human whole blood and exudate cells taken from mice.
What Were the Study Results?
The research team discovered that the local anesthetic lidocaine impairs resolution of inflammation. In contrast, the inhaled anesthetic isoflurane promotes resolution of inflammation.
The cellular-level experiments showed that lidocaine increases the accumulation of white blood cells in the area of inflammation, impairs the natural dieing-off of polymorphonuclear cells (PMNs; also called neutrophils) that occurs during resolution, and hampers the removal of dead PMNs from the site of inflammation. The experiments also showed that isoflurane reduced the infiltration of neutrophils to the site of inflammation and accelerated resolution by regulating the production of beneficial mediators.
Serhan states, “The results of the present studies demonstrate that lidocaine imposes a molecular lesion in resolution that delays the return to homeostatis while isoflurane accelerates resolution and the return to homeostasis.”
What Does this Mean for People Facing Surgery?
The findings of this study bring to light consequences of lidocaine use that have not been considered before. Lidocaine’s inhibition of the resolution pathway may have far-reaching clinical implications, according to Serhan. He concludes, “The results of the present study offer new avenues, not only for continued studies in the cellular and molecular markers in resolution of inflammation, but also for future clinical research.”
Chiang N, Schwab JM, Fredman G, et al. Anesthetics impact the resolution of inflammation. PLoS ONE 2008;3(4):e1879.
Read how foods can impact inflammation at Arthritis Today.