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The quinoline-3-carboxamide paquinimod (ABR-215757) reduces leukocyte recruitment during sterile inflammation: Leukocyte- and context-specific effects.

Deronic, Adnan LU ; Helmersson, Sofia LU ; Leanderson, Tomas LU and Ivars, Fredrik LU (2014) In International Immunopharmacology 18(2). p.290-297
Abstract
Quinoline-3-carboxamides (Q-compounds) are currently in clinical development for both autoimmune disease and cancer. We have previously shown that the Q-compound paquinimod (ABR-215757) significantly ameliorates disease symptoms in several mouse models of human inflammatory disease. Considering that recruitment of inflammatory cells into tissue is a common denominator of these models, we have in this report investigated whether paquinimod would interfere with cell accumulation during sterile peritoneal inflammation. To mimic the cell recruitment elicited by tissue injury, we used necrotic cells to induce the acute inflammatory response. We show that per oral treatment with paquinimod significantly reduced the accumulation of Ly6C(hi)... (More)
Quinoline-3-carboxamides (Q-compounds) are currently in clinical development for both autoimmune disease and cancer. We have previously shown that the Q-compound paquinimod (ABR-215757) significantly ameliorates disease symptoms in several mouse models of human inflammatory disease. Considering that recruitment of inflammatory cells into tissue is a common denominator of these models, we have in this report investigated whether paquinimod would interfere with cell accumulation during sterile peritoneal inflammation. To mimic the cell recruitment elicited by tissue injury, we used necrotic cells to induce the acute inflammatory response. We show that per oral treatment with paquinimod significantly reduced the accumulation of Ly6C(hi) inflammatory monocytes and eosinophils, but not neutrophils, in this model, and that this correlated with reduced number of such cells also in the omentum. Treatment also reduced the accumulation of these cell populations at a subcutaneous site of inflammation. In alum-induced inflammation, however, neutrophils were the dominant cell population and paquinimod failed to reduce the accumulation of inflammatory cells. Taken together, our results indicate that paquinimod selectively inhibits cell recruitment during acute sterile inflammation, but that this effect is context-dependent. These data have important implications for the understanding of the mechanism of action of Q-compounds in both pre-clinical and clinical settings. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
International Immunopharmacology
volume
18
issue
2
pages
290 - 297
publisher
Elsevier
external identifiers
  • pmid:24370393
  • wos:000331412900013
  • scopus:84891766095
ISSN
1878-1705
DOI
10.1016/j.intimp.2013.12.008
language
English
LU publication?
yes
id
a3332cc2-5f64-48dd-a2f7-5aec33f74d6a (old id 4222968)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24370393?dopt=Abstract
date added to LUP
2014-01-06 13:42:01
date last changed
2017-01-08 03:33:29
@article{a3332cc2-5f64-48dd-a2f7-5aec33f74d6a,
  abstract     = {Quinoline-3-carboxamides (Q-compounds) are currently in clinical development for both autoimmune disease and cancer. We have previously shown that the Q-compound paquinimod (ABR-215757) significantly ameliorates disease symptoms in several mouse models of human inflammatory disease. Considering that recruitment of inflammatory cells into tissue is a common denominator of these models, we have in this report investigated whether paquinimod would interfere with cell accumulation during sterile peritoneal inflammation. To mimic the cell recruitment elicited by tissue injury, we used necrotic cells to induce the acute inflammatory response. We show that per oral treatment with paquinimod significantly reduced the accumulation of Ly6C(hi) inflammatory monocytes and eosinophils, but not neutrophils, in this model, and that this correlated with reduced number of such cells also in the omentum. Treatment also reduced the accumulation of these cell populations at a subcutaneous site of inflammation. In alum-induced inflammation, however, neutrophils were the dominant cell population and paquinimod failed to reduce the accumulation of inflammatory cells. Taken together, our results indicate that paquinimod selectively inhibits cell recruitment during acute sterile inflammation, but that this effect is context-dependent. These data have important implications for the understanding of the mechanism of action of Q-compounds in both pre-clinical and clinical settings.},
  author       = {Deronic, Adnan and Helmersson, Sofia and Leanderson, Tomas and Ivars, Fredrik},
  issn         = {1878-1705},
  language     = {eng},
  number       = {2},
  pages        = {290--297},
  publisher    = {Elsevier},
  series       = {International Immunopharmacology},
  title        = {The quinoline-3-carboxamide paquinimod (ABR-215757) reduces leukocyte recruitment during sterile inflammation: Leukocyte- and context-specific effects.},
  url          = {http://dx.doi.org/10.1016/j.intimp.2013.12.008},
  volume       = {18},
  year         = {2014},
}