Fig. 1. Ketoprofen efficacy in a preclinical model of lymphedema can be attributed to its inhibition of LTB4. Ketoprofen efficacy in a preclinical model.

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LTB4 production is elevated in preclinical and clinical lymphedema

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Volume 37, Issue 4, Pages (October 2012)

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LTB4 production is elevated in preclinical and clinical lymphedema

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Fig. 1. Ketoprofen efficacy in a preclinical model of lymphedema can be attributed to its inhibition of LTB4. Ketoprofen efficacy in a preclinical model of lymphedema can be attributed to its inhibition of LTB4. (A) Mouse tail model of acquired lymphedema was surgically induced in the tails of female C57BL/6J mice through thermal ablation of lymphatic trunks (lymphatic surgery). Skin incision alone was performed in the sham surgery group (sham). (B) Natural progression of mouse tail model of lymphedema. Tail volume at each measurement time point was calculated as Δ volume from day 0. Cartoon representations of the cross-sectional view of lymphedematous tails were created to illustrate lymphedema progression. Mice without surgery (control) or sham groups were compared to the categories subjected to lymphatic surgery; n = 8. (C) Overview of the eicosanoid pathway. Therapies, targeting different eicosanoid pathways, tested in the study were marked in blue. (D to J) Serial tail volume measurements at each time point over 24 days. Treatments targeting both 5-LO and COX1/2 (ketoprofen, n = 15) (D), 5-LO (zileuton, n = 10) (F), LTA4H (bestatin, n = 14) (H), BLT1 (Ly293111, n = 10) (I), or Ltb4r1 (local administering of lentiviral shLtb4r1, n = 6) (J) were compared with ibuprofen (inhibits COX1/2, n = 13) (E) and montelukast (antagonizes CysLT, n = 10) (G) therapies. All therapies started on postsurgical day 3. Cartoon representations in red demonstrate the cross-sectional view of the lymphedematous tails in the saline-treated groups; cartoon in blue illustrates the eicosanoid inhibitor–treated animals after lymphatic ablation. Quantification of dermal (K) and epidermal (L) skin thickness and lymphatic area (M) in the day 24 mouse tail skin for (D) to (J); n = 5. In (B) and (D) to (M), data are presented as means and SEM; ns, not significant, Kruskal-Wallis test followed by Dunn’s multiple comparisons test for post hoc analyses. Wen Tian et al., Sci Transl Med 2017;9:eaal3920 Published by AAAS