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01-02-2018 | Original Article

Dual neutralization of TNFR-2 and MMP-2 regulates the severity of S. aureus induced septic arthritis correlating alteration in the level of interferon gamma and interleukin-10 in terms of TNFR2 blocking

Authors: Sahin Sultana, Rajen Dey, Biswadev Bishayi

Published in: Immunologic Research | Issue 1/2018

Abstract

Severity of S. aureus septic arthritis is correlated to prolonged inflammation by inflammatory cytokines like TNF-α, IL-1β, and IL-6 even after successful elimination of bacteria. Role of TNF-α via TNFR2 is not well established in this aspect. IFN-γ induces TNF-α release from the macrophages augmenting the inflammatory arthritis. IL-10 modulates the levels of pro-inflammatory cytokines promoting resolution of inflammation. TNF-α-TNFR2 signaling upregulates both of these cytokines. Higher level of MMP-2 induction by inflammatory cytokines during arthritis promotes tissue destruction. Whether dual neutralization of TNFR-2 and MMP-2 regulates the severity of S. aureus arthritis by modulating local and systemic cytokine milieu mainly due to TNFR-2 blocking was an obvious question. Here, we attempted the effects of neutralization of MMP-2 and TNFR2 on S. aureus arthritis and its impact on pro-inflammatory cytokines and some other parameters related to tissue destruction. Reduction in arthritis index was noticed in infected mice treated with both MMP-2 inhibitor and TNFR2 antibody. Lowest levels of inflammatory cytokines, iNOS, RANKL, NF-κb, JNK kinase, ROS, and MPO, and lysozyme activity were observed in combined neutralization group at 9 and 15 dpi, but at 3 dpi, most of the above parameters remained elevated due to TNFR2 neutralization. Diminished IL-10 and IFN-γ levels as a result of TNFR2 neutralization at early and later phase of infection respectively might be responsible for these contrasting effects. Overall, it can be suggested that administration of MMP-2 inhibitor and TNFR2 antibody in combination is protective against the inflammation and tissue destruction associated with S. aureus infection during the arthritic episode.

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Title: Dual neutralization of TNFR-2 and MMP-2 regulates the severity of S. aureus induced septic arthritis correlating alteration in the level of interferon gamma and interleukin-10 in terms of TNFR2 blocking
Authors: Sahin Sultana
Rajen Dey
Biswadev Bishayi
Publication date: 01-02-2018
Publisher: Springer US
Published in: Immunologic Research / Issue 1/2018
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-017-8979-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Dual neutralization of TNFR-2 and MMP-2 regulates the severity of S. aureus induced septic arthritis correlating alteration in the level of interferon gamma and interleukin-10 in terms of TNFR2 blocking

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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