Possible Involvement of Interleukin‐1 in Cyclooxygenase‐2Induction After Spinal Cord Injury in Rats

A standardized compression injury of rat spinal cord brought about a time-dependent biphasic production of thromboxane A 2 (detected as thromboxane B 2 ) and prostaglandin I 2 (detected as 6-ketoprostaglandin F 1α ). Thromboxane B 2 was predominant during the first 1 h, whereas the 6-ketoprostaglandin F 1α level exceeded that of thromboxane B 2 at 8 h postinjury. As examined by inhibitor experiments and northern blotting, cyclooxygenase-1 was responsible for the first phase, and cyclooxygenase-2 was involved in the second phase. On compression injury the levels of interleukin-1α and -1β detected as mRNA and protein increased and peaked at 2-4 h. Injection of exogenous interleukin-1 α into the spinal cord resulted in an increase of cyclooxygenase-2 mRNA content and a predominant production of 6-keto-prostaglandin F 1α resembling the second phase of eicosanoid production. Concomitantly, extravascular migration of polymorphonuclear leukocytes was enhanced after the interleukin-1α injection. These cells together with vascular endothelial cells and glial cells were stained positively with an anti-cyclooxygenase-2 antibody. The results suggest that the immediate eicosanoid synthesis after spinal cord injury was due to the constitutive cyclooxygenase-1 and the delayed synthesis of eicosanoids was attributable to the induction of cyclooxygenase-2 mediated by interleukin-1α.