IL-2 and regulation of stress hormones and BDNF neurotropic factor levels after experimental traumatic brain injury (TBI)

Experimental traumatic brain  injury  (TBI)   causes  a  stable  stress  response   and  changes   the expression  of various cytokine genes and neurotrophic factors.  The goal of this study was to reveal changes  in the  levels of the  corticosterone and  testosterone hormones and  the  BDNF cytokine in blood  serum,  as well as the expression  of the BDNF gene in hypothalamus in order  to determine the opportunity of correcting the TBI damage  with rIL-2. We used a rat model  of “dropping load”:  mild TBI was caused  by falling of the 115 g load from the height  of 80 cm,  or 120 cm to produce a moderate-degree trauma. After TBI (immediately, or 72 hours  later), the  rats were injected daily with recombinant human interleukin-2 (Roncoleukin) at a dose of 30 μg/kg, a total  of 3 injections. Control animals  (also with TBI)  received  0.15 M NaCl  injections. Blood serum  concentrations of corticosterone, testosterone, and  BDNF were measured with ELISA  tests.  BDNF gene expression in hypothalamus was measured using RT-PCR. Results: the experiments showed a relationship between  hormone concentrations and severity of head injury. In mild TBI,  blood corticosterone levels reached a peak  2 hours  after the  injury, while in moderate TBI,  the  peak  concentration of corticosterone was lower, being delayed  in time  (after  24 hours). Corticosterone and  testosterone concentrations changed reciprocally in the both groups of injured  animals. With injection of rIL-2 in both groups,  corticosterone and testosterone levels were significantly  increased. On  day 7 after  TBI,  the  BDNF level in blood  serum  was decreased, but it was raised  in experimental group  that  received  rIL-2. On day 7, the increase  of BDNF gene expression  in hypothalamus was more  pronounced, when  rIL-2 was administered at 72 hours  after  the  head  injury.  The revealed  positive  association of BDNF levels and  glucocorticoid hormones after  mild  TBI,  like as possible coordination of these  parameters with rIL-2 injection after experimental moderate TBI  provides  a reason  to assume  that  the favorable  impact of rIL-2 on the CNS  recovery  after TBI is, in part,  mediated by the mutual modulating interaction of BDNF and glucocorticoid hormones.