TIME COURSE OF SYSTEMIC AND BRAIN CYTOKINE EXPRESSION BY ENDOTOXIN AND ROLE OF DEXAMETHASONEAbstract
Literature evidence suggests that neuroinflammation plays a key role that activates and propagates the neurodegenerative process associated with many neurological diseases. Different stimuli, such as lipopolysaccharide (LPS) are the endotoxin that activates the immune system to create neuroinflammation associated with neurodegeneration. The peak expression of different cytokines (TNF-α, IL-1β & IL-6) post LPS injection is time-dependent. Those inflammatory cytokines in plasma and the brain were measured by enzyme-linked immune sorbent assay (ELISA). To inhibit the cytokine expression, the mice were orally given a single dose (1 mg/kg) of Dexamethasone (Dexa), 0.5 h prior to LPS injection. Above cytokines were observed at their peak expression time points and the plasma & brain concentrations of Dexa were analysed using LC-MS/MS. Brain/plasma ratio (B/P) was calculated. Our results indicate that Dexa (1 mg/kg, po) has better anti-inflammatory effect in plasma with good exposure and minimal efficacy in brain may be due to low B/P ratio.
Shuvranshu Praharaj *, V. K. Kalaichelvan, V. Murugan and Ishtiyaque Ahmad
Jubilant Biosys Ltd, Bangalore, College of Pharmaceutical Sciences, Bangalore, Karnataka, India.
24 April 2021
24 June 2021
28 June 2021
01 February 2022