Abstract
Ropivacaine, a new local anesthetic, is currently being investigated for the treatment of ulcerative colitis, with promising results so far. The aim of this study was to examine anti-inflammatory properties of ropivacaine with regard to its effects on vascular permeability and inflammatory leukocyte behavior in vivo. The effects on leukocyte rolling, firm adhesion and vascular permeability were examined in the hamster cheek pouch microvasculature viaintravital microscopy, and the effects on leukocyte adhesion molecules were examined in vitro by means of flow cytometry. In large venules, leukocyte adhesion induced by topical leukotriene B4 (LTB4) was almost completely inhibited during the combined application of ropivacaine and LTB4. The spontaneous rolling leukocyte flux was reduced by 72%, the rolling leukocyte fraction by 47% and the total leukocyte flux, which reflects blood flow, by 47%. In postcapillary venules, ropivacaine abolished rolling and LTB4-induced firm adhesion of leukocytes. LTB4 challenge also resulted in increased plasma exudation that was almost completely inhibited by ropivacaine. Moreover, ropivacaine inhibited the tumor necrosis factor α-induced up-regulation of CD11b/CD18 and L-selectin shedding by human leukocytesin vitro. Our results suggest that ropivacaine exerts anti-inflammatory activity, and this appears to be mediated to a significant extent by inhibition of both leukocyte rolling and adhesion.
Footnotes
-
Send reprint requests to: Titti Martinsson, Astra Pain Control AB, Preclinical R&D, Novum Unit, S-141 57 Huddinge, Sweden.
-
↵1 This study was supported by grants from the National Associations for the Prevention of Asthma and Allergy, the Swedish Medical Society, Consul Th. C. Berghs Foundation, the Swedish Work Environment Fund and the Swedish Medical Research Council (grant no. 16X-105).
- Abbreviations:
- FITC
- fluorescein isothiocyanate, fMLP, formyl-methionyl-leucyl-phenylalanine
- LTB4
- leukotriene B4, MFI, mean fluorescence intensity
- PBS
- phosphate-buffered saline
- PE
- phycoerythrin
- TNF-α
- tumor necrosis factor α
- UC
- ulcerative colitis
- Received March 6, 1997.
- Accepted June 30, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|