Interaction between interleukin-6 and the natural anticoagulant system in acute stroke

Inflammatory reactions mediated by cytokines are involved in the pathogenes is of acute stroke. Decrease in circulating levels of protein C (PC) and pr otein S (PS) induced by inflammatory cytokines has been postulated as a pot ential mechanism for a procoagulant tendency during acute stroke. The proco agulant state associated with impairments in natural anticoagulants may in; luce microvascular obstruction leading to a tissue perfusion reduction that worsens cerebral ischemia, Interleukin-6 (IL-6) regulate the synthesis of C4b-binding protein (C4BP), an acute-phase protein that also regulates PS p lasma levels. We measured IL-6, C4BP, erythrocyte sedimentation rate (ESR), total and free PS and PC in 44 patients with acute ischemic stroke to dete rmine if IL-6 decreases circulating levels of natural anticoagulants throug h the C4BP pathway and if these acute changes in natural anticoagulants may have clinical implications. Patients with higher levels of IL-6 had more s evere neurologic deficits on admission, greater infarct size, higher levels of acute-phase reactants, and lower levels of free PS, IL-6 was significan tly correlated with C4BP, ESR, and free PS levels. PC levels were also lowe r in the group of patients with greater IL-6, but differences were not stat istically significant. No correlations were found between C4BP and natural anticoagulants, Severe neurologic deficit, greater infarct volume, atrial f ibrillation, increased levels of inflammatory parameters (ESR and IL-6), an d reduced levels of free PS were associated with disabling stroke at 3 mont hs, but only neurologic severity and ESR remained as independent predictors of stroke disability on multiple regression analysis. Inflammatory reactio ns mediated by IL-6 during:the acute phase of stroke influence the modulati on of free PS, However, variations in free PS levels do not have implicatio ns for clinical outcome in stroke patients. The link between proinflammator y cytokines and free PS in the acute phase of stroke is not related to the C4BP pathway.