PMID- 12056513
OWN - NLM
STAT- MEDLINE
DCOM- 20021129
LR  - 20191106
IS  - 1023-3830 (Print)
IS  - 1023-3830 (Linking)
VI  - 51
IP  - 5
DP  - 2002 May
TI  - Amelioration of rat adjuvant arthritis by therapeutic treatment with bindarit, an 
      inhibitor of MCP-1 and TNF-alpha production.
PG  - 252-8
AB  - OBJECTIVE: This study was designed to evaluate therapeutic effects of bindarit, 
      an indazolic derivative able to inhibit monocyte chemoattractant protein-1 
      (MCP-1) production, in adjuvant induced arthritis in rats. MATERIALS AND METHODS: 
      Arthritis was induced by Freund's complete adjuvant injection. Bindarit was given 
      as a 0.5% medicated diet starting on day 11 after adjuvant injection. The course 
      of arthritis was monitored by sequential paw volume measurement and by radiologic 
      and histologic evaluations. Human osteoblast cell line Saos-2 stimulated with 
      Interleukin-1 (IL-1) was used to assess in vitro bindarit effect on MCP-1 
      release. In addition, in vivo effects of bindarit on cytokine production were 
      studied in mice injected with lipopolysaccharide (LPS). Immune function studies 
      were performed in mice by evaluating ex vivo antibody response to ovalbumin and 
      splenocytes proliferation to Concanavalin A (Con A). RESULTS: In adjuvant-induced 
      arthritis in rats, bindarit possessed therapeutic activity resulting in a 
      significant inhibition of paw inflammation. Evidence for a disease-modifying 
      activity was also indicated by amelioration of radiologic alterations and by 
      histological evaluation of joints. Additional evidence for beneficial effects in 
      osseous inflammation was provided by an in vitro assay in which bindarit 
      inhibited the release of MCP-1 from IL-1 stimulated osteoblast cells. Moreover, 
      in a murine model of LPS-induced cytokine production bindarit reduced MCP-1 and 
      tumor necrosis factor (TNF)-alpha increase without affecting IL-1 and IL-6 
      levels. Finally, the drug, given as a 0.5% medicated diet for 14 days, did not 
      affect either anti-ovalbumin serum antibody production or splenocytes 
      proliferative response in mice. CONCLUSIONS: Results obtained indicate that 
      bindarit beneficial effects in experimental arthritis are correlated to MCP-1 and 
      TNF-alpha inhibition and suggest that the control of cytokines and chemokines 
      production can have considerable relevance as regards strategies for the 
      treatment of chronic inflammatory diseases.
FAU - Guglielmotti, A
AU  - Guglielmotti A
AD  - Immunopharmacology Lab, ACRAF SpA - Angelini Ricerche, Rome, Italy. 
      rd.guglielmotti@angelini.it
FAU - D'Onofrio, E
AU  - D'Onofrio E
FAU - Coletta, I
AU  - Coletta I
FAU - Aquilini, L
AU  - Aquilini L
FAU - Milanese, C
AU  - Milanese C
FAU - Pinza, M
AU  - Pinza M
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Indazoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Propionates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9006-59-1 (Ovalbumin)
RN  - JQ11LH711M (bindarit)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/diagnostic imaging/*drug therapy/pathology
MH  - Cell Line
MH  - Chemokine CCL2/*antagonists & inhibitors/biosynthesis
MH  - Cytokines/biosynthesis
MH  - Hindlimb/pathology
MH  - Humans
MH  - Immunity/drug effects
MH  - Indazoles/*therapeutic use
MH  - Lipopolysaccharides
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Osteoblasts/drug effects
MH  - Ovalbumin/immunology
MH  - Propionates/*therapeutic use
MH  - Radiography
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/biosynthesis
EDAT- 2002/06/12 10:00
MHDA- 2002/11/30 04:00
CRDT- 2002/06/12 10:00
PHST- 2002/06/12 10:00 [pubmed]
PHST- 2002/11/30 04:00 [medline]
PHST- 2002/06/12 10:00 [entrez]
AID - 10.1007/pl00000301 [doi]
PST - ppublish
SO  - Inflamm Res. 2002 May;51(5):252-8. doi: 10.1007/pl00000301.