Expression of Leukotrienes is Increased in Human MS and in a Mouse Adoptive Transfer Model of MS (B98)

Abstract

Abstract Leukotrienes are well established as mediators of inflammation, however little is known regarding their role in the pathogenesis of multiple sclerosis (MS). In humans, elevated LTA4-h levels were reported in acute inflammatory lesions of a single primary progressive (PP) patient, while increased mRNA and protein levels of 5-lipoxygenase were seen in both PP-MS and relapsing remitting (RR) patients. LTB4 levels were higher in the cerebrospinal fluid of patients with active MS compared to controls, while levels of cysteinyl leukotrienes LTC4, LTD4, and LTE4 were not different. Beyond these preliminary disease association data, little is known about role of leukotrienes in MS. BLT1, the high affinity receptor for LTB4, has recently been reported to be expressed on both human and mouse antigen-experienced T lymphocytes. We show here that encephalitogenic T cells specific for a myelin antigen express functional BLT1. When transferred into naïve recipients these T cells are sufficient to induce disease. In addition, peripheral blood T cells from RR-MS patients express altered levels of the BLT1 receptor as compared to normal healthy controls. In the CNS, we show that demyelinating plaques in human MS brain tissues have up-regulated levels of LTA4-h and BLT1 by immunohistochemistry suggesting involvement of this pathway in the pathogenesis of MS and highlighting potential new targets for therapeutic intervention.