Anti-Inflammatory Characteristics of Local Anesthetics: Inhibition of TNF-α Secretion of Lipopolysaccharide-Stimulated Leucocytes in Human Blood Samples

Abstract

Background. Local anesthetics (LAs) have potent anti-inflammatory properties. Inflammatory down-regulation is crucial in diseases with overactive immune reactions, such as acute respiratory distress syndrome (ARDS) and chronic inflammation. We investigated the influence of four LAs, procaine, lidocaine, mepivacaine, and bupivacaine, on the reduction of tumor necrosis factor-alpha (TNF-α) secretion in lipopolysaccharide (LPS)-activated human leucocytes. Methods. Blood samples of 28 individuals were stimulated with LPS. The reduction of TNF-α production by each of the four LAs added (0.5 mg/mL) was measured and correlated with biometric variables. A response was defined as reduction to <85% of initial levels. Results. All four LAs down-regulated the TNF-α secretion in 44–61%: Bupivacaine (44.4%), lidocaine (61.5%), mepivacaine (44.4%), and procaine (50% of the individuals, “responders”). The TNF-α secretion was reduced to 67.4, 68.0, 63.6, and 67.1% of the initial values in responders. The effects in both patients and healthy persons were the same. Interindividual responses to LAs were not correlated with the duration or type of complaints, basal TNF-α serum level, sex, BMI, or age of responders. Conclusions. Four clinically relevant LAs (amid-LA and ester-LA) attenuate the inflammatory response provoked by LPS. They are potential candidates for drug repositioning in treating overactive immune reactions and chronic inflammation.

Improvement in post-orthodontic chronic musculoskeletal pain after local anesthetic injections in the trigeminal area: a case series

“…Procaine was chosen as the LA because of its rapid metabolism (metabolized by plasma cholinesterases), high safety profile, low neurotoxicity, sympatholytic effects, favorable effects on the microcirculation, and short half-life. 21 The modulating effects of LAs on the immune system have been described in the medical literature. The main mechanisms of action that have been proposed are leukocyte inhibition, decreased inflammatory mediators, and decreased vascular hyperpermeability and edema formation.…”

Intravenous Lidocaine in Non-Opioid Multimodal Perioperative Pain Management: Current Controversy and Future Perspectives

“…lidocaineсамата статия]. However, just a few human studies demonstrate the anti-inflammatory properties of lidocaine in reducing the surgery-induced release of pro-inflammatory cytokines IL-1, IL-6, IL-8, and TNF-α [55][56][57][58], or the TNF-α production in lipopolysaccharide-activated human leukocytes [59].…”

The Use of Intravenous Lidocaine in Perioperative Medicine: Anaesthetic, Analgesic and Immune-Modulatory Aspects

“…A recent study in 2022 [ 44 ] investigated the effect of local anaesthetics on tumour necrosis factor-alpha (TNF-α) secretion. TNF-α normally plays an important role in inflammation and carcinogenesis.…”