Evaluation of the disease modifying activity of Colchicum luteum Baker in experimental arthritis.
ABSTRACT Colchicum luteum (CL) has been traditionally used in the Unani system of medicine as a chief ingredient of many polyherbal formulations for the treatment of joint pain and rheumatoid arthritis (RA).
To evaluate the antiarthritic activity of CL hydroalcoholic extract (CLHE) in formaldehyde and complete Freund's adjuvant (CFA) induced arthritis.
Arthritis was induced by administration of either formaldehyde (2% v/v) or CFA into the subplantar surface of the hind paw of the animal. Joint swelling was measured on days 8, 9 and 10 in formaldehyde induced arthritis and days 3, 7, 14 and 21 in CFA induced arthritis. In order to evaluate the effect of CLHE on disease progression, serum TNF-α level and synovial expression of proinflammatory mediators (TNF-R1, IL-6 and IL-1β) was determined in CFA induced arthritis.
CLHE produced a significant and dose dependent inhibition of joint swelling during the entire duration of the study in both, formaldehyde and CFA induced arthritis. Serum TNF-α level was also reduced significantly in a dose dependent manner in all the CLHE treated groups. The expression of proinflammatory mediators (TNF-R1, IL-6 and IL-1β) was also found to be less in the CLHE treated group as compared to control.
We believe that the antiarthritic activity of CLHE was due to its modulatory effect on the expression of proinflammatory cytokine in the synovium. Our results contribute towards validation of the traditional use of CL in the treatment of RA and other inflammatory joint disorders.
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ABSTRACT: To develop and evaluate a new immunohistochemical method to study the localisation and phenotype of individual cytokine producing cells in synovial biopsy specimens in rheumatoid arthritis. Cryopreserved sections of synovial tissue from nine patients with rheumatoid arthritis were incubated with carefully selected cytokine specific antibodies detecting 19 different cytokines, after fixation of the specimens with paraformaldehyde and using saponin to permeabilise the cell membranes. The immunohistochemical method yielded reproducible and distinct staining patterns, in which the cytokines accumulated mainly in the Golgi apparatus of producer cells, indicating that the method preferentially detected local synthesis rather than cytokine uptake. The cytokine production patterns varied considerably between biopsy specimens from different patients. The present modified immunohistochemical method may provide a simple and rapid way to determine the local production of a wide array of cytokines in the synovium. The data obtained with this method also indicated that more T cell derived cytokines than previously recognised were present in active synovitis, as located and sampled by arthroscopy.Annals of the Rheumatic Diseases 09/1995; 54(8):654-61. · 9.11 Impact Factor
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ABSTRACT: Activation of macrophages by LPS and taxol results in production of IL-1, IL-6, TNF-alpha, and granulocyte-macrophage CSF (GM-CSF), which are involved in regulating hemopoiesis, inflammation, and immune responses. Microtubules are proposed as a target site for LPS interaction(s), based on similarities between the effects of the tubulin-binding drug taxol and LPS. To clarify the role of microtubules in LPS-induced GM-CSF expression in macrophages, we examined whether microtubule depolymerizing agents affect GM-CSF production in macrophages. Pretreatment with colchicine impaired LPS induction of GM-CSF in RAW 264 cells, and studies using stable transfectants revealed that colchicine impaired the transcriptional responsiveness of a reporter gene driven by a GM-CSF promoter sequence. Colchicine inhibition of the GM-CSF response correlated with decreases in the mRNA levels of beta-tubulin; maximal inhibition of both events was observed 4 h after addition of colchicine. Microtubule agents inhibited LPS induction of IL-6 and TNF-alpha, while the induction of both IL-1beta and inducible nitric oxide synthase was unaltered, suggesting that LPS activates microtubule-dependent and -independent pathways. Interestingly, LPS stimulation of macrophages down-regulated levels of beta-tubulin transcripts, implying that LPS interacts with an element(s) of the microtubule network in vivo, activating pathways regulating transcription of beta-tubulin. The ability of both colchicine and LPS to modulate transcription of beta-tubulin suggests that this event does not per se underlie the inhibitory effect of colchicine on LPS-induced GM-CSF expression. These data led us to conclude that colchicine inhibits LPS induction of GM-CSF by affecting microtubule-dependent costimulatory signaling pathways that synergize with primary LPS-triggered responses.The Journal of Immunology 11/1997; 159(7):3531-9. · 5.52 Impact Factor