Format

Send to

Choose Destination
Mod Rheumatol. 2015 Jul;25(4):562-70. doi: 10.3109/14397595.2014.983262. Epub 2015 Mar 24.

Modulation of immunological responses and amelioration of collagen-induced arthritis by the novel roxithromycin derivative 5-I.

Author information

1
Division of Clinical Immunology, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo , Minato-ku, Tokyo , Japan.

Abstract

OBJECTIVE:

Macrolide antibiotics have immunomodulatory properties that are distinct from their antibacterial functions. We synthesized 5-I, which is a new derivative of RXM with less antimicrobial activity, and evaluated its immunomodulatory effects through both in vitro and in vivo studies.

METHODS:

Proliferative response, cytokine production, and expression of mRNA of T cells stimulated with anti-CD3 and anti-CD28 mAbs in the presence or absence of monocytes, cytokine production of monocytes stimulated with lipopolysaccharide, and transendothelial migration of T cells in various concentrations of 5-I were analyzed. The effect of 5-I treatment was also evaluated in a mouse model of collagen-induced arthritis.

RESULTS:

5-I specifically inhibited production of Th1, Th17, and proinflammatory cytokines such as IL-2, IFN-γ, TNF-α, IL-6, and IL-17A. 5-I reduced the expression of RORC on CD4(+) T cells, which codes for RORγt, the master regulator of Th17, and it also inhibited migration of activated T cells. Importantly, administration of 5-I to mice with collagen-induced arthritis reduced the severity of arthritis, and this effect was also observed when treatment was delayed till after the onset of disease.

CONCLUSION:

Our findings strongly suggest that 5-I may be useful as a potential therapeutic agent for human rheumatoid arthritis.

KEYWORDS:

5-I; Collagen-induced arthritis; Monocytes; Rheumatoid arthritis; Roxithromycin; T cells

PMID:
25800509
DOI:
10.3109/14397595.2014.983262
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center