Progesterone and allopregnanolone reduce inflammatory cytokines after traumatic brain injury.

Abstract Following a traumatic brain injury (TBI), the excessive release of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) is a major cause of cerebral edema, which, in turn, can cause permanent neuronal loss and cognitive deficits in laboratory rats. This study examined the changes in expression of the proinflammatory cytokines IL-1β and TNF-α after progesterone (8 mg/kg) or allopregnanolone (4 mg/kg) treatment in brain-injured rats at 3, 8, and 12 h and 6 days post-injury. Adult male rats received either bilateral prefrontal cortical contusion or sham surgery. The hormones were given intraperitoneally at 1 and 6 h, and continued once per day for up to 5 days. The gene expression of IL-1β and TNF-α was measured by mRNA using real-time quantitative reverse transcripted polymerase chain reaction (RT-PCR). The protein concentrations of IL-1β and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA) to confirm the translation from mRNA to protein. The results indicated that progesterone and allopregnanolone reduce both IL-1β and TNF-α at 3 h post-injury, when the expression of these cytokines peaks. At 8 and 12 h post-injury, IL-1β and TNF-α gene expression in injured rats was still elevated compared to shams. By the sixth day post-injury, cytokine expression was back to the level of intact rats. We conclude that progesterone and allopregnanolone may attenuate the production of proinflammatory cytokines early after TBI, and this may be one mechanism by which progesterone and allopregnanolone reduce cerebral edema and promote functional recovery from TBI.