Influence of the course of brain inflammation on the endogenous IL-1β/IL-1Ra balance in the model of brain delayed-type hypersensitivity response to bacillus Calmette-Guérin in Lewis rats

Interleukin-1β (IL-1β) is a key player in the pathogenesis of acute and chronic inflammatory diseases at the periphery and in the brain. Its action is regulated by interleukin-1 receptor antagonist (IL-1Ra), the specific endogenous antagonist of IL-1 receptors. The ratio between local concentrations of IL-1Ra and IL-1β is known to influence the initiation and progression of many inflammatory and autoimmune diseases at the periphery. In order to determine whether this is also the case in the brain, brain and plasma concentrations of IL-1β and IL-1Ra were measured by ELISA in a model of chronic brain inflammation in Lewis rats, the hippocampal delayed-type hypersensitivity (DTH) response to bacillus Calmette-Guérin (BCG). Brain IL-1β increased rapidly after intracerebral (i.c.) injection of BCG and came back to baseline concentrations 1 week later, whereas IL-1Ra increased gradually over time and remained elevated during the last 2 weeks post-BCG intracerebral injection. Following peripheral BCG challenge, brain IL-1β increased at the site of the brain BCG and peaked 12 days later before decreasing on day 16 post-challenge. Brain IL-1Ra remained elevated during the first days post-challenge and then decreased from the 12th day post-challenge. The same temporal variations were observed in the plasma concentrations of IL-1β and IL-1Ra. The increase in the IL-1β/IL-1Ra ratio that was apparent from day 3 to day 12 post-challenge might be correlated with the invasion of peripheral inflammatory cells at the site of intracerebral injection. Besides showing that the course of inflammation alters the brain IL-1β/IL-1Ra ratio, these findings point to the importance of monitoring plasma IL-1β/IL-1Ra ratio to predict the course of brain inflammation.