Antibody-based targeted delivery of interleukin-4 synergizes with dexamethasone for the reduction of inflammation in arthritis

Schmid, Anja Sophie, Hemmerle, Teresa, Pretto, Francesca, Kipar, Anja ORCID: 0000-0001-7289-3459 and Neri, Dario (2018) Antibody-based targeted delivery of interleukin-4 synergizes with dexamethasone for the reduction of inflammation in arthritis. RHEUMATOLOGY, 57 (4). pp. 748-755.

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Official URL: http://dx.doi.org/10.1093/rheumatology/kex447

Abstract

<h4>Objectives</h4>We have previously reported that F8-IL4, a fusion protein consisting of the F8 antibody specific to the alternatively-spliced extra domain A of fibronectin and of murine IL-4, cures mice with established arthritis, when used in combination with dexamethasone (DXM). The goal of this study was to assess whether other therapeutic agents, besides DXM, could induce cures in combination with F8-IL4 and to elucidate which leucocytes are most affected by the pharmacological treatment.<h4>Methods</h4>We performed therapy experiments in mice with CIA, using intravenous administrations of F8-IL4 in combination with DXM, MTX, murine cytotoxic T-lymphocyte-associated protein 4 fused to the fragment crystallizable portion of murine IgG2a, as well as mAbs to murine IL17A or the p40 subunit of murine IL12/IL23. Histology and immunohistochemistry for the identification of the various leucocytes were performed on the paws of mice euthanized at different therapy time points.<h4>Results</h4>Only the use of F8-IL4 in combination with DXM induced complete remissions, while all other combinations did not lead to cures. The light microscopical evaluation of paws with arthritis revealed a predominant infiltration of neutrophils, which substantially decreased 24 h after treatment with F8-IL4 and DXM.<h4>Conclusion</h4>The combination of F8-IL4 with DXM promotes a rapid anti-arthritic action by potently inhibiting neutrophil activity. A fully human analogue of F8-IL4 may find clinical utility for the treatment of neutrophil-driven chronic inflammatory conditions.

Item Type:	Article
Uncontrolled Keywords:	collagen-induced arthritis, interleukin-4, immunocytokines, EDA of fibronectin, Type II interleukin-4 receptor, neutrophils
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	14 May 2021 13:28
Last Modified:	18 Jan 2023 22:47
DOI:	10.1093/rheumatology/kex447
Open Access URL:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC61048...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3122711