CEREBROSPINAL-FLUID INTERLEUKIN-1 RECEPTOR ANTAGONIST AND TUMOR-NECROSIS-FACTOR-ALPHA FOLLOWING SUBARACHNOID HEMORRHAGE

Subarachnoid hemorrhage (SAH) causes an inflammatory reaction and may lead to ischemic brain damage. Experimental ischemia has been shown to be connected with the alarm-reaction cytokines interleukin-1 receptor antagonist (IL-1Ra) and tumor necrosis factor-alpha (TNF alpha). Incr eased levels of these cytokines, however, have not been detected thus far in patients following an SAH event. For this reason daily cerebros pinal fluid (CSF) samples were collected from 22 consecutively enrolle d patients with SAH and from 10 non-SAH patients (controls). The CSF s amples were studied using immunoassays for IL-1Ra and TNF alpha to inv estigate whether an SAH caused increased cytokine levels. The mean IL- 1R alpha levels were significantly higher in patients with SAH who wer e in poor clinical condition on admission than in those who were in go od condition (318 pg/ml vs. 82 pg/ml, p < 0.02). The IL-1Ra levels inc reased during delayed ischemic episodes and after surgery in patients who were in poor clinical condition. Significant increases in IL-1Ra a nd TNF alpha were detected during Days 4 through 10 in patients suffer ing from SAH who eventually had a poor outcome (p < 0.05). Patients wi th good outcomes and control patients had low levels of these cytokine s. The levels of IL-1Ra increased after surgery in patients with Hunt and Hess Grades III through V, but not in those with Grade I or II. Th is finding indicates that patients in poor clinical condition have a l abile biochemical state in the brain that is reflected in increased cy tokine levels following the surgical trauma. Both IL-1Ra and TNF alpha are known to induce fever, malaise, leukocytosis, and nitric oxide sy nthesis and to mediate ischemic and traumatic brain injuries. The pres ent study shows that levels of these cytokines increase after SAH occu rs and that high cytokine levels correlate with brain damage. It is th erefore likely that fever, leukocytosis, and nitric oxide synthesis ar e also mediated by IL-l in patients suffering from SAH and it is proba ble that the inflammatory mediators contribute to brain damage.