title: Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage.
abstract: Subarachnoid hemorrhage (SAH) elicits an inflammatory response in the subarachnoid space, which is mediated by the release of various cytokines. To assess their involvement in post-hemorrhagic complications, we determined the source and time-course of the release of inflammatory cytokines and acute-phase proteins in cerebrospinal fluid (CSF) following SAH. Concentrations of interleukin (IL)- 1beta, IL-6, transforming growth factor-beta1 (TGF-beta1) and C-reactive protein (CRP) in CSF of 36 patients with SAH were measured by enzyme-linked immunoabsorbent assay (ELISA). Floating cells collected from the CSF were centrifuged four to six days after SAH, and examined immunohistochemically. Intracellular IL-1beta and IL-6 were examined by flow cytometric analysis. The molecular weight of TGF-beta1 in CSF of 30 patients was examined by Western blot analysis. The TGF-beta1 levels of patients who had undergone ventriculoperitoneal (VP) shunt (n = 19) was significantly higher than nonshunt group (n = 16). The CRP levels of VP shunt group was significantly higher than nonshunt group. IL-6 concentration was maximal within day 0-1 and it was secreted by neutrophils and monocytes. ELISA showed consistently low levels of IL-1beta, whereas a proportion of monocytes and lymphcytes were IL- 1beta-positive by flow cytometric analysis. TGF-beta1 levels were also maximal on day 0-1 according to ELISA, although it tended to be in the inactive form derived from platelets. A 25 kDa band of TGF-1 was detectable for at least 13 days after SAH, which may have been secreted in part by neutrophils and monocytes. CRP levels in CSF peaked on day 2-3. The present results suggest that leukocytes induced by SAH play an important role in post-hemorrhagic inflammation in the subarachnoid space by releasing IL-6 and TGF-beta1. The CRP and TGF-beta1 levels in CSF are strongly concerned with communicating hydrocephalus after SAH.
authors.affiliation: Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto, Japan. taki777@hsp.md.shinshu-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Takizawa
authors.forename: T
authors.initials: T
authors.lastname: Tada
authors.forename: K
authors.initials: K
authors.lastname: Kitazawa
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Hongo
authors.forename: M
authors.initials: M
authors.lastname: Kameko
authors.forename: K I
authors.initials: KI
authors.lastname: Uemura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000134:cerebrospinal fluid / Q000276:immunology; D002555:Cerebrospinal Fluid / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D016207:Cytokines / Q000134:cerebrospinal fluid* / Q000276:immunology; D004660:Encephalitis / Q000134:cerebrospinal fluid* / Q000209:etiology* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000134:cerebrospinal fluid / Q000276:immunology; D015850:Interleukin-6 / Q000134:cerebrospinal fluid / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000134:cerebrospinal fluid / Q000276:immunology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D002097:C-Reactive Protein