Hyperthermia is a surrogate marker of inflammation-mediated cause of brain damage in acute ischaemic stroke.
The influence of temperature on the outcome observed in experimental models of ischaemic stroke has not been definitively proved in patients with stroke. Interleukin-6 (IL-6) acts as important endogenous pyrogen, and it is an important regulator of spontaneous body temperature during cerebral ischaemia. The objective of this study was to determine, during the acute phase of cerebral ischaemia, the potential relationship between proinflammatory cytokines and hyperthermia as a cause of larger cerebral infarcts.


METHODS
We studied 229 patients with a first-ever acute hemispheric infarction admitted within the first 24 h from onset of symptoms. On admission, axillary temperature was recorded and blood chemistry studies and cranial computed tomography were performed. We classified body temperature into two groups: hyperthermia (>or=37.5 degrees C) and normothermia (<37.5 degrees C). We determined proinflammatory markers [IL-6, tumour necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule (ICAM-1) and vascular cellular adhesion molecule] on admission. Two outcome variables were evaluated: (i) infarct volume; (ii) Canadian Stroke Scale (CSS) at 3 months (CSS <or= 7 was considered poor outcome and CSS > 7 good outcome).


RESULTS
Patients with hyperthermia had higher infarct volume [46.5 (9.8-78.5) cm(3) vs. 19.1 (5.0-23.5) cm(3); P < 0.0001], as well as poor outcome at 3 months. Plasma levels of IL-6, TNF-alpha and ICAM-1 were significantly higher in the group of patients with hyperthermia than in the normothermic group. There was a significant correlation between body temperature on admission and infarct volume (r = 0.302; P < 0.0001), and between proinflammatory markers (IL-6 and TNF-alpha) and infarct volume. A significant association was also found between proinflammatory markers (IL-6, TNF-alpha, and ICAM-1) and poor outcome. However, after adjustment for potential confounders, hyperthermia was not independently associated with either larger infarct volume or with poor outcome at 3 months.


CONCLUSIONS
Inflammatory mediators play a role in acute ischaemic brain damage independently of hyperthermia.
Leira
R
R
Department of Neurology, Stroke Unit and Neurovascular Research Laboratory, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Rodríguez-Yáñez
M
M
Castellanos
M
M
Blanco
M
M
Nombela
F
F
Sobrino
T
T
Lizasoain
I
I
Dávalos
A
A
Castillo
J
J
D000208:Acute Disease; D000368:Aged; D001831:Body Temperature; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications; D015815:Cell Adhesion Molecules / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D005260:Female; D005334:Fever / Q000097:blood*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000097:blood* / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015815:Cell Adhesion Molecules; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1