Arthritis is inhibited in Borrelia-primed and infected interleukin-17A-deficient mice after administration of anti-gamma-interferon, anti-tumor necrosis factor alpha and anti-interleukin-6 antibodies

Joseph Kuo; Thomas F Warner; Ronald F Schell

doi:10.1093/femspd/ftx073

Arthritis is inhibited in Borrelia-primed and infected interleukin-17A-deficient mice after administration of anti-gamma-interferon, anti-tumor necrosis factor alpha and anti-interleukin-6 antibodies

Pathog Dis. 2017 Aug 31;75(6). doi: 10.1093/femspd/ftx073.

Authors

Joseph Kuo^{1

2}, Thomas F Warner³, Ronald F Schell^{1

2

4}

Affiliations

¹ Wisconsin State Laboratory of Hygiene, University of Wisconsin-Madison, Madison, WI 53706, USA.
² Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
³ Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53792, USA.
⁴ Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.

PMID: 28859307
DOI: 10.1093/femspd/ftx073

Abstract

The role that cytokines play in the induction of Lyme arthritis is gradually being delineated. We showed previously that severe arthritis developed in a T-cell-driven murine model, even in mice lacking interleukin-17A (IL-17A) and administered anti-gamma-interferon (IFN-γ) antibody. Increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), two pro-inflammatory cytokines, were detected in cultures of popliteal lymph node cells obtained from these mice. We hypothesized that concomitantly administered anti-IL-6, anti-TNF-α and anti-IFN-γ antibodies would inhibit the development of arthritis in IL-17A-deficient mice. Our results showed that swelling of the hind paws and histopathological changes consistent with arthritis were significantly reduced in IL-17A-deficient mice that administered the three anti-cytokine antibodies. These results suggest that treatment with multiple anti-cytokine antibodies can abrogate the induction of Lyme arthritis in mice.

Keywords: Borrelia burgdorferi; Lyme arthritis; T cells; gamma-interferon; interleukin-17A; interleukin-6; tumor necrosis factor alpha.

Publication types

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

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology*
Antibodies / pharmacology*
Borrelia burgdorferi / growth & development
Borrelia burgdorferi / pathogenicity
Disease Models, Animal
Gene Expression
Hindlimb / drug effects
Hindlimb / immunology
Hindlimb / microbiology
Hindlimb / pathology
Interferon-gamma / antagonists & inhibitors*
Interferon-gamma / genetics
Interferon-gamma / immunology
Interleukin-17 / deficiency
Interleukin-17 / genetics
Interleukin-17 / immunology
Interleukin-6 / antagonists & inhibitors*
Interleukin-6 / genetics
Interleukin-6 / immunology
Lyme Disease / drug therapy*
Lyme Disease / immunology
Lyme Disease / microbiology
Lyme Disease / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / immunology

Substances

Anti-Inflammatory Agents
Antibodies
Interleukin-17
Interleukin-6
Tumor Necrosis Factor-alpha
interleukin-6, mouse
Interferon-gamma