Protection against Experimental Allergic Encephalomyelitis with Complete Freund’s Adjuvant Is Unaffected by Prostaglandin Synthesis Inhibition

Abstract

Pretreatment with complete Freund’s adjuvant blended with aluminium hydroxide (ALU-CFA) prevents the clinical as well as histological manifestation of experimental allergic encephalomyelitis (EAE) in Lewis rats. Suppression of prostaglandin biosynthesis with the cyclooxygenase inhibitor piroxicam (10 mg/kg body weight) from day 2 before to day 17 after EAE induction could not restore responsiveness in pretreated animals. In contrast piroxicam increased ALU-CFA-induced suppression of autoantibodies against myelin basic protein. In controls not pretreated with ALU-CFA, clinical signs of EAE were attenuated by piroxicam, whereas mononuclear infiltration of the brain remained unchanged. Therefore it is unlikely that prostaglandins exert an important function in the regulation of immune responses in this model of autoimmunity.

Experimental Allergic Encephalomyelitis – Prophylactic and Therapeutic Treatment with the Cyclooxygenase Inhibitor Piroxicam (Feldene®)

“…In a previous publication, we reported that the prophylactic application of piroxicam (Feldene®), a reversible inhibitor of cyclooxygenase, attenuated clinical signs of EAE, although the cellular infiltra tion of the central nervous system was not altered [3], The following investigation confirms these results and shows the effects of a therapeutic administration of piroxicam at the clinical and histological level. Pos sible reasons for the different effects of the prophy lactic and therapeutic treatment are discussed.…”

“…EDl-positive cells in the circumference of the infiltrate were counted. b Significance of results was calculated using Wilcoxon's rank test [15], EAE, the permeability of the blood-brain-barricr is increased by the encephalogenic mixture, which allows hydrophilic molecules to enter the central nervous system [15], In a previous study [3], we reported that the clin ical signs of EAE were attenuated by the prophylactic administration of piroxicam. These results were con firmed by our experiments reported here.…”

Developing therapeutics for the treatment of multiple sclerosis

“…COX-2 expression was also colocalized to iNOS expression, particularly in regions showing active demyelination, suggesting that COX-2 inhibitors could have therapeutic application in MS. As a result of these findings, recently developed COX-2 inhibitors, effective in the treatment of conditions such as inflammatory pain and rheumatoid arthritis, are now being investigated for a broader range of disease indications, including Parkinson's disease, ALS, stroke and AD. 62 In terms of disease-relevance to MS, nonselective COX inhibitors (BW755c, piroxicam, phenidone), as well as anti-PGE antibodies, have shown prophylactic effects in models of EAE, 60,[63][64][65] suggesting that the COX-2 component may play a prominent role in the inflammatory pathological cascade of MS. The results from the report, of CNS localization of COX-2 in the brains of MS patients and EAE-sensitized animals, highlights the potential importance of COX-2 in the pathogenesis of MS.…”