Impact of Anesthetics on Immune Functions in a Rat Model of Vagus Nerve Stimulation

Abstract

Vagus nerve stimulation (VNS) has been successfully performed in animals for the treatment of different experimental models of inflammation. The anti-inflammatory effect of VNS involves the release of acetylcholine by vagus nerve efferent fibers inhibiting pro-inflammatory cytokines (e.g. TNF-α) produced by macrophages. Moreover, it has recently been demonstrated that splenic lymphocytic populations may also be involved. As anesthetics can modulate the inflammatory response, the current study evaluated the effect of two different anesthetics, isoflurane and pentobarbital, on splenic cellular and molecular parameters in a VNS rat model. Spleens were collected for the characterization of lymphocytes sub-populations by flow cytometry and quantification of cytokines secretion after in vitro activation. Different results were observed depending on the anesthetic used. The use of isoflurane displayed a non-specific effect of VNS characterized by a decrease of most splenic lymphocytes sub-populations studied, and also led to a significantly lower TNF-α secretion by splenocytes. However, the use of pentobarbital brought to light immune modifications in non-stimulated animals that were not observed with isoflurane, and also revealed a specific effect of VNS, notably at the level of T lymphocytes’ activation. These differences between the two anesthetics could be related to the anti-inflammatory properties of isoflurane. In conclusion, pentobarbital is more adapted than isoflurane in the study of the anti-inflammatory effect of VNS on an anesthetized rat model in that it allows more accurate monitoring of subtle immunomodulatory processes.

Baroreflex stimulation attenuates central but not peripheral inflammation in conscious endotoxemic rats

“…A significant exception can be attributed to Martelli and colleagues (Martelli et al, 2014a) who demonstrated, in conscious rats, that the splanchnic anti-inflammatory pathway has a powerful and sustained inhibitory influence on inflammatory processes. It is well known that anesthetics interfere particularly with the neural mechanisms modulating the immune system (Picq et al, 2013). For instance, several studies showed that ketamine and isoflurane exhibit potent anti-inflammatory properties (Flondor et al, 2008; Hofstetter et al, 2005; Qin et al, 2015).…”

Immune Modulation by Volatile Anesthetics

“…In general, volatile anesthetics induced a decrease in proliferation of lymphocytes or an increase in lymphocyte apoptosis. 9,119–121 …”

Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis

“…Moreover, anesthetic drugs interfere with the neuronal activation and they also showed anti-inflammatory properties. As consequence, these properties may not represent a real effect of nerve stimulation in a systemic inflammatory condition [51]. Another limitation of using the electrical vagus nerve stimulation in sepsis therapies involves the high rates of splenic lymphocytes apoptosis.…”