Changes And Their Clinical Study Of Cytokines In Patients With Multiple Organ Dysfunction Syndrome After Actue Cerebrovascular Disease

Background: Multiple organ dysfunction syndrome(MODS) is the presence of altered organ function in acutely ill patients such that homeostasis cannot be maintained without intervention. It usually involves two or more organ systems. It is a hot topic for its complicated pathogenesis, difficult treatment and high mortality in medical science. Acute cerebral vascular disease(ACVD) is a common and frequently encountered disease which jeopardises the heath of human. ACVD, coronary heart disease and malignant tumor are the top three fetal diseases in the world. As medicine advances, more and more patients avoid dying of primary cerebral damage (cerebral hernia, central respiratory and circulatory failure). But many patients suffered from ACVD undergo MODS, and it becoms the major cause of death. The pathogenesis of MODS secondary to ACVD is not very clear, it is thought to be loss of control of inflammatory response– breaking the balance of systemic inflammatory and anti-inflammatory responses.It is very hard to cure when the patients undergo MODS, so it is very important to detect sensitive indexes which can assess and be treated of the severe ACVD after MODS patients.Objective: To investigate the clinical features of ACVD complicated with MODS, study the pathogenesis, investigate the changes and clinical significance of serum anti-inflammatory cytokine–tumor necrosis factor- alpha(TNF-α), pro-inflammatory–cytokineinterleukin-6(IL-6),anti-inflamma- tory cytokine–interferon-γ(IFN-γ) and persistent inflammatory cytokine–high mobility group box-1 (HMGB-1).Methods: All 59 subjects in this prospective cohort study with ACVD were enrolled in the Neurology Department and Neurosurgery Department of the NO.1 Clinical Hospital of Jinlin University from 12-2006 to 11-2007, and were hospitalized within 3 days and proved with head CT or MRI scan. All the MODS patients were diagnosed by the criteria of Multiple Organ Dysfunction Syndrome with Illness Severity Score System,and according to this criteria, all the subjects were divided to two groups : the MODS group and the simple ACVD group. There were 28 patients in MODS group:16 men and 12 women ,10 had cerebral hemorrhage,16 had cerebral infarction, and 2 had subarachnoid hemorrhage,age 29～83,[mean] 63.5±14.1) and 31 simple ACVD patients(19 men and 12 women ,10 had cerebral hemorrhage,18 had cerebral infarction, and 3 had subarachnoid hemorrhage,age 32～86,[mean] 63.2±11.9). All 28 control samples were from Medical Examination Center: 15men and 13 women, age 27～79,[mean] 60.7±13.2. All the patients were assessed by Multiple Organ Dysfunction Syndrome with Illness Severity Score System, Glasgow Coma Scale (GCS) and NIHSS score, and the detailed information of every case including patients'age, sex, the type of strokes, primary chronic diseases, the multiple disordered organs, number of disordered organs, life signs and laboratory examinations, complications and prognosis etc. was recorded.Blood was collected the next morning after the patients enrolled, allowed to clot at room temperature for 15min, then spun at 12,000 rmp for 5min, and sera collected for storage at–70°C.After all the sample collected, by using fluorescent detection of Western blot the semiquantitative HMGB-1 levels were detected, and serum TNF-α,IL-6, IFN-γlevels were measured by ABC- ELISA .Results:1.The GCS and NIHSS scores between the groups of MODS and simple ACVD patients were significantly different, and mortality of MODS after ACVD was 42.86%, higher than who didn't have MODS(14.81%).The most disordered organs were stomach and bowel. The morbidity of 3 disordered organs was the highest in MODS group, and the mortality of 6 disordered organs was the highest.The mean score of the MODS Illness Severity Score was 6.892±2.183, and the highest mortality was the group 10~12. 2. The serum HMGB-1 levels were significantly elevated as compared with the simple ACVD group and the healthy volunteers, and they were positive correlation with the MODS scores. 3. The serum TNF-αlevels were significantly elevated compared with the other groups with the mean level of 106.783±71.866 pg/ml, the simple ACVD group was the second, and the lowest mean level of TNF-αwas the group of the healthy volunteers. 4. The serum IL-6 levels were significantly elevated compared with the other groups with the mean level of 81.142±76.823 pg/ml, the simple ACVD group was the second, and the lowest mean level of IL-6 was also the group of the healthy volunteers. 5.There was not significant difference between the groups of MODS and simple ACVD in IFN-γlevels, but both of them were higher than the group of the healthy volunteers. 6.No striking diversity was found between the cerebral hemorrhage and infarction patients of MODS group in the HMGB-1,TNF-α,IL-6 and IFN-γlevels.Conclusions: 1. The mortality of MODS after ACVD was significantly higher than simple ACVD patients', and MODS secondary to ACVD is the main death cause in cerebral vascular patients. 2. The primary cerebral diseases of MODS after ACVD patients were severe and could effect other organs. Stomach and bowel were the most disordered organs of MODS after ACVD patients. 3.The criteria of Multiple Organ Dysfunction Syndrome with Illness Severity Score System could be used to assess the stage of illness, so it could be used to assess the patients'conditions , and instruct the clinical treatment. 4. The HMGB-1,TNF-αand IL-6 levels were significantly elevated suggest that one of the pathogenesis of MODS secondary to ACVD is out control of SIRS/CARS balance. 5.The serum levels of anti-inflammatory cytokine–TNF-α, pro-inflammatory cytokine–IL-6, and persistent inflam- matory cytokine–HMGB-1 were significantly elevated suggest that they can be used for sensitive indexes of MODS after ACVD. MODS after ACVD might be obstructed by interfering HMGB-1 which is a persistent inflammatory cytokine and positive correlation with the MODS scores. 6. The IFN-γlevels were not significantly elevated compared with simple ACVD patients, suggest that IFN-γparticipates in the pathophysiology of acute cerebral vascular disease,but might not be released significantly after MODS secondary to ACVD.