Modulation of bioavailability of proinflammatory cytokines produced by myeloid cells

Maxim A Nosenko; Kamar-Sulu N Atretkhany; Vladislav V Mokhonov; Ekaterina A Vasilenko; Andrei A Kruglov; Sergei V Tillib; Marina S Drutskaya; Sergei A Nedospasov

doi:10.1016/j.semarthrit.2019.09.012

Modulation of bioavailability of proinflammatory cytokines produced by myeloid cells

Semin Arthritis Rheum. 2019 Dec;49(3S):S39-S42. doi: 10.1016/j.semarthrit.2019.09.012.

Authors

Maxim A Nosenko¹, Kamar-Sulu N Atretkhany¹, Vladislav V Mokhonov², Ekaterina A Vasilenko³, Andrei A Kruglov⁴, Sergei V Tillib⁵, Marina S Drutskaya⁶, Sergei A Nedospasov⁷

Affiliations

¹ Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; Lomonosov Moscow State University, Moscow 119234, Russia.
² Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; Lobachevsky University of Nizhni Novgorod, Nizhni Novgorod 603950, Russia.
³ Lobachevsky University of Nizhni Novgorod, Nizhni Novgorod 603950, Russia.
⁴ Lomonosov Moscow State University, Moscow 119234, Russia; German Rheumatism Research Center (DRFZ), Leibniz Institute, Berlin 10117, Germany.
⁵ Institute of Gene Biology, Russian Academy of Sciences, Moscow 119991, Russia.
⁶ Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
⁷ Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; Lomonosov Moscow State University, Moscow 119234, Russia. Electronic address: sergei@nedos.net.

PMID: 31779851
DOI: 10.1016/j.semarthrit.2019.09.012

Abstract

In spite of successful therapeutic neutralization of proinflammatory cytokines in several autoimmune diseases, such therapy is not entirely free of side effects. The main reason relates to the fact that cytokine signaling may have protective components that need to be spared. Several approaches to achieve a less damaging cytokine inhibition are being explored. In our experimental studies we are using bispecific reagents based on VHH-modules from the heavy-chain-only antibodies to limit bioavailability of TNF and IL-6 produced by myeloid cells. After evaluation of their properties in vitro and in vivo we argue that these types of reagents may have an advantage over systemic blockers.

Keywords: Bispecific antibodies; CD11b; F4/80; IL-6; TNF; VHH.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoimmune Diseases / immunology
Autoimmune Diseases / metabolism*
Autoimmunity*
Biological Availability
Cytokines / metabolism*
Humans
Myeloid Cells / metabolism*

Substances

Cytokines