Conversely, inhibition of TNF-α and IL-1β by hypertonicity was found to be beneficial in cerebral edema, and the functional role of TNF-α and IL-1β in the regulation of NKCC1 expression was validated in vitro, leading the authors to propose that TNF-α and IL-1β may directly upregulate NKCC1 expression via JNK- and p38-dependent pathways (67). This evidence concerns the gene SLC12A2 and brain edema.