Blaho VA et al. – Early production of COX-2 products is necessary for resolution of the inflammatory arthritis induced by Borrelia infection, and that COX-2 inhibition may result in prolonged inflammatory states, possibly by inhibition of proresolution eicosanoids. Methods
Study to determine the contribution of COX-2 to temporal regulation of the inflammatory response to infection in a murine model of Lyme arthritis
Experimental Lyme disease was induced in both arthritis-resistant DBA/2J and arthritis-susceptible C3H/HeJ mice by inoculation in the hind footpads with Borrelia burgdorferi
COX-2 inhibitors were administered daily, and their effect on arthritis pathology was assessed at various time points postinfection ,/li>
The COX-2 deficiency was also backcrossed onto both DBA and C3H backgrounds to confirm the findings from COX-2 inhibitor-treated mice
Results
In COX-2 inhibitor-treated or COX-2-/- C3H mice, arthritis developed normally but did not resolve
Cessation of COX-2 inhibitor treatment on day 14 postinfection did not induce resolution of arthritis, indicating an early onset
The lack of resolution of arthritis correlated with altered COX-2 and cytosolic phospholipase A2 mRNA levels in the joints of C3H mice
In addition, the proresolution lipid molecule 15-deoxy-Δ12,14-prostaglandin J2 was produced in response to B burgdorferi infection, and its production was attenuated by the inhibition of COX-2
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