Anti-IL-6 cytokine treatment has no impact on elevated hematocrit or splenomegaly in a polycythemia vera mouse model.

Abstract

Somatic mutations in JAK2, MPL and Calreticulin and inflammation play a key role in pathophysiology of chronic myeloproliferative neoplasia (CMN). One of the most prominent cytokines elevated in serum of Polycythemia vera patients is interleukin-6 (IL-6). Currently, it is being discussed whether suppression of inflammation by anti-cytokine approaches as anti-IL-6 treatment may be therapeutically useful in CMN. We here sought to investigate the efficacy of anti-IL-6 treatment on inflammatory cytokines, hematocrit and splenomegaly in CMN like disease. JAK2-V617F knock-in mice (JAK2+/V617F) were treated for three weeks with anti-IL-6 antibody (Ab) or IgG-control. Upon anti-IL-6 Ab treatment, serum levels of CXCL2 and CXCL10 were significantly reduced. In addition, CXCL1, CCL11, M-CSF, G-CSF, IL-17, IL-12p40 and CCL2 were reduced by a factor of 0.3 -- 0.8. Partly, this was also achieved by applying high-dose IgG. Hematocrit, erythrocyte and leukocyte counts were elevated in JAK2+/V617F mice but were not reduced by anti-IL6 Ab treatment. In addition, there was no apparent amelioration of splenomegaly and spleen histopathology. In conclusion, anti-IL-6 Ab treatment did not result in improvement of hematological disease parameters but was shown to modulate the serum cytokine signature.

• Authors: Conny K Baldauf, Peter Müller, Tobias R Haage, Stephanie Adam-Frey, Juliane Lokau, Christoph Garbers, Thomas Fischer
• Journal: Blood advances (Blood Adv) Vol. 6 Issue 2 Pg. 399-404 (01 25 2022) ISSN: 2473-9537 [Electronic] United States
• PMID: 34559181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• Cytokines
• Immunoglobulin G
• Interleukin-6

Topics

• Animals
• Cytokines
• Disease Models, Animal
• Hematocrit
• Humans
• Immunoglobulin G (therapeutic use)
• Inflammation
• Interleukin-6
• Mice
• Myeloproliferative Disorders (drug therapy)
• Polycythemia Vera (complications, drug therapy, genetics)
• Splenomegaly (drug therapy, etiology)