Roxithromycin specifically inhibits development of collagen induced arthritis and production of proinflammatory cytokines by human T cells and macrophages.
OBJECTIVE
Roxithromycin (RXM) is a macrolide antibiotic that is effective in treatment of chronic lower respiratory tract diseases including diffuse panbronchiolitis and bronchial asthma. Its mechanism of action apart from its antibacterial action remains unclear. To determine the mechanism of action of RXM, we evaluated the effect of RXM on T cell functions and the inflammatory responses in mice with collagen induced arthritis (CIA).


METHODS
T cell proliferation, cytokine production by T cells stimulated through CD28, CD26, or PMA with or without anti-CD3 Mab, cytokine production by macrophages stimulated with lipopolysaccharide, and transendothelial migration of T cells were analyzed in the presence or absence of various concentrations of RXM. We evaluated the effect of RXM treatment in collagen induced arthritis in mice.


RESULTS
RXM did not affect the production of Th1-type and Th2-type cytokines, whereas it specifically inhibited production of proinflammatory cytokines such as tumor necrosis factor-a and interleukin 6 (IL-6) by T cells and macrophages. RXM inhibited T cell migration. We found that RXM treatment of mice with CIA reduced the severity of arthritis and serum level of IL-6, as well as leukocyte migration into the affected joints and destruction of bones and cartilage.


CONCLUSIONS
Our findings strongly suggest that RXM may be useful for the therapy of rheumatoid arthritis as well as other inflammatory diseases such as Crohn's disease.
Urasaki
Yasuyo
Y
Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
Nori
Mamoru
M
Iwata
Satoshi
S
Sasaki
Takahiro
T
Hosono
Osamu
O
Kawasaki
Hiroshi
H
Tanaka
Hirotoshi
H
Dang
Nam H
NH
Ikeda
Eiji
E
Morimoto
Chikao
C
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001707:Biopsy, Needle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011336:Probability; D015575:Roxithromycin / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015575:Roxithromycin; D003094:Collagen