title: The quinoline-3-carboxamide paquinimod (ABR-215757) reduces leukocyte recruitment during sterile inflammation: leukocyte- and context-specific effects.
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.
authors.affiliation: Immunology Group, Section for Immunology, Department of Experimental Medical Science, Lund University, Sweden. Electronic address: adnan.deronic@med.lu.se.
authors.forename: Adnan
authors.initials: A
authors.lastname: Deronic
authors.affiliation: Immunology Group, Section for Immunology, Department of Experimental Medical Science, Lund University, Sweden. Electronic address: sofia.helmersson@med.lu.se.
authors.forename: Sofia
authors.initials: S
authors.lastname: Helmersson
authors.affiliation: Immunology Group, Section for Immunology, Department of Experimental Medical Science, Lund University, Sweden. Electronic address: tomas.leanderson@med.lu.se.
authors.forename: Tomas
authors.initials: T
authors.lastname: Leanderson
authors.affiliation: Immunology Group, Section for Immunology, Department of Experimental Medical Science, Lund University, Sweden. Electronic address: fredrik.ivars@med.lu.se.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ivars
mesh_terms: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology*; D011804:Quinolines / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D039481:CD11b Antigen; D007166:Immunosuppressive Agents; D011804:Quinolines; C041524:aluminum sulfate; C573440:paquinimod
keywords: Immunomodulation; Inflammation; Monocyte; Omentum; Peritoneum; Quinoline-3-carboxamide