To investigate the role of IMs that infiltrate into the CNS after chronic alcohol, we used a small molecule inhibitor, cenicriviroc (CVC), that blocks the chemokine receptors CCR2 and CCR5, receptors expressed on monocytes and macrophages, among other immune cells [16, 21]. Some mice were fed chronic alcohol and were treated daily with CVC throughout alcohol exposure for a total of 6 weeks of treatment (6wk CVC), while other mice fed chronic alcohol were only treated with CVC for the final 3 weeks (3wk CVC), mimicking a clinical treatment paradigm where treatment often begins only after exposure has occurred (Fig. 3a). Pair-fed and alcohol-fed mice received daily vehicle control injections. Alcohol significantly increased CD11b+CD45hi IMs compared to pair-fed controls (Fig. 3b). Both 6wk CVC and 3wk CVC treatment paradigms abrogated the alcohol-induced infiltration of CD11b+CD45hi IMs, significantly reducing IMs to the level of pair-fed mice (Fig. 3b, c).
