Restoration of depressed immune function in spinal cord injury patients receiving rehabilitation therapy.

Both natural and adaptive immune responses were strikingly decreased 2 weeks after injury in 49 spinal cord injuries, 28 tetraplegic and 21 paraplegic patients compared to agematched controls. All values are expressed as means. NK cell function decreased to 21.0% 2 weeks after spinal cord injury compared to 48.6% in controls. At 2 weeks, plasma ACTH values increased to 17.0 pg/ml in patients compared to 11.2 pg/ml in controls and urine free cortisol levels were elevated to 162.4 micrograms/24 h in patients compared to 53.6 ug/24 h in controls. T cell function decreased to 40.2% of normal (lymphocyte transformation) by 3 months post injury. T cell activation (IL-2R) was diminished, i.e., 183.4 ug/ml compared to 328.2 ug/ml in controls. With rehabilitation therapy, NK cell function increased to 41.6% by 7 months post injury. NK cell-mediated lysis diminished sharply between 7 and 9 months decreasing to 22.8% at 10 months and ultimately returning to the 2 week post injury level. Rehabilitation therapy contributed to the restoration of T cell function to 92.0% of normal by 6 months post injury where it remained for 6+ months. IL-2R values improved in parallel with lymphocyte transformation. Whereas NK cell-induced lysis remained depressed, i.e., 11.8% at 6 months and 11.4% at 12+ months in patients not receiving therapy, the restoration of NK cell function at 6 months to 40.6% in rehabilitated patients decreased to 23.0% with cessation of treatment. NK cell-mediated lysis values in cervical injury patients were significantly less than those in the thoracic injury group. FIM scores of the two paralleled their NK cell function. With rehabilitation therapy, NK cell-mediated lysis in the cervical group increased from 15.2% to 28.4%, whereas it improved in the thoracic group with therapy from 26.8% to 43.7%. With rehabilitation therapy, lymphocyte transformation in the cervical group increased from 37.3% to 85.6% and improved in the thoracic group from 48.4% to 88.9%. With rehabilitation therapy, FIM scores improved from 49.7 to 74.0 in the cervical group and from 79.8 to 97.3 in thoracic patients compared to 126 in controls of healthy age matched controls.

Decreased immune reactivity and neuroendocrine alterations related to chronic stress in spinal cord injury and stroke patients.

Both natural and adaptive immune responses were found to be strikingly decreased 2 weeks after injury in 54 spinal cord injury and stroke patients, i.e., 28 quadriplegics, 21 paraplegics and 5 stroke patients, compared with those of age-matched controls. All values are expressed as means. Natural-killer (NK)-cell function decreased to 21.0% 2 weeks after spinal cord injury compared with 48.6% in controls. At 2 weeks, plasma ACTH values increased to 17.0 pg/ml in patients compared with 11.2 pg/ml in controls, and urine free cortisol levels were elevated to 162.4 micrograms/24 h in patients compared with 53.6 micrograms/24 h in controls. T-cell function decreased to 40.2% of normal (lymphocyte transformation) by 3 months after injury. T-cell activation (IL-2R) was diminished, i.e., 183.4 micrograms/ml compared with 328.2 micrograms/ml in controls. With rehabilitation therapy, NK-cell function increased to 41.6% by 7 months after injury. NK-cell-mediated lysis diminished sharply between 7 and 9 months, decreasing to 22.8% at 10 months and ultimately returning to the level seen 2 weeks after injury. Rehabilitation therapy contributed to the restoration of T-cell function to 92.0% of normal by 6 months after injury where it remained for 6+ months. IL-2R values improved in parallel with lymphocyte transformation. Whereas NK-cell-induced lysis remained depressed, i.e., 11.8% at 6 months and 11.4% at 12+ months in patients not receiving therapy, the restoration of NK-cell function at 6 months to 40.6% in rehabilitated patients decreased to 23.0% with cessation of treatment. NK-cell-mediated lysis values in cervical injury patients were significantly less than those in the thoracic injury group. Functional independence measurement (FIM) scores of the two paralleled their NK-cell function. With rehabilitation therapy, NK-cell-mediated lysis in the cervical group increased from 15.2 to 28.4%, whereas it improved in the thoracic group with therapy from 26.8 to 43.7%. With rehabilitation therapy, lymphocyte transformation in the cervical group increased from 37.3 to 85.6% and improved in the thoracic group from 48.4 to 88.9%. With rehabilitation therapy, FIM scores improved from 49.7 to 74.0 in the cervical group and from 79.8 to 97.3 in thoracic patients compared with 126 in controls. NK-cell-mediated lysis was depressed to 28.9% in 5 stroke patients and improved to 38.0% following rehabilitation therapy.

Neuroendocrine-immune interactions associated with loss and restoration of immune system function in spinal cord injury and stroke patients.

Both natural and adaptive immune responses were shown to be strikingly decreased in initial blood samples from 34 spinal cord injury and stroke patients. NK-cell function decreased to 24.8% (mean) 2 weeks after spinal cord injury in previously healthy young adults whose control group revealed a mean NK-cell function of 48.7%. This was accompanied at 2 weeks by increased plasma ACTH (mean of 17.0 pg/ml from 17 patients compared to a mean of 11.2 pg/ml from 12 controls) and urine free cortisol levels (mean of 152.1 micrograms/24 h from 9 patients compared to 53.6 micrograms/24 h from 15 controls). T-cell function and/or activation decreased to below normal values within 3 months after injury as revealed by lymphocyte transformation that was 32.8% of normal at 3 months. T-cell activation diminished as shown by a mean IL-2 receptor level of 179.3 units/ml in patients compared to 328.2 units/ml in controls. Serial monitoring of NK- and T-cell function revealed that specific physical rehabilitation therapy over a period of 6 months after injury restored NK- and T-cell function to near normal levels in most patients. This improvement was accompanied by a parallel rise in the patient's functional independence measurement scores. Results suggest critical neuroendocrine-immune system interactions in the restoration of immune function. Cortisol levels reverted to normal after 6 months of rehabilitation. Limited data suggest that natural immune system depression, NK-cell function, persists in spinal cord injury patients not receiving rehabilitation therapy (mean NK-cell lysis of 10.3%; p < 0.01).