Involvement of steroids and cytochromes P450 species in the triggering of immune defenses

In vertebrates the wide variety of cytochromes P450 (P450) is a key for elimination of low molecular weight xenobiotics and for the production and metabolism of steroid hormones. In contrast, xenobiotics of large molecular weight are processed and eliminated after the immune response. The suppression of immune response by native P450-produced glucocorticoid (GC) hormones constitutes a first link between P450 and immunity. In the last decade, mechanisms and molecules responsible for the triggering of immune response were investigated and results showed that many tissues and organs transform native 3β-hydroxysteroids into 7-hydroxylated metabolites that trigger immunity. Present data suggest that 7-hydroxysteroids are native anti-GCs that block the GC-induced immunosuppression. Because specific P450 are responsible for the production of 7-hydroxylated steroids resulting into increased immunity, a second link exists between P450 and immunity. Taken together, these findings support the proposal that P450 are keys to all of the known defense mechanisms of vertebrates against all xenobiotic forms. [Copyright &y& Elsevier]