TY - JOUR
T1 - Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inhaled from tobacco smoke
AU - Whitehouse, Michael Wellesley
AU - Jones, Mark
PY - 2009/10
Y1 - 2009/10
N2 - Objective: To seek a mechanism linking tobacco smoking with the increased incidence and severity of rheumatoid arthritis, deduced from many retrospective surveys, by studying arthritis/fibrosis development in rats. Methods: Rats (>300) received low levels of sodium/potassium thiocyanate (10 or 25 mmol/l) in their drinking water to raise their blood thiocyanate levels, mimicking the elevated levels of blood, salivary and urinary thiocyanate found in smokers. Results: Thiocyanate supplements increased the severity of experimental arthritis induced by tailbase injection of (1) Freund's complete adjuvants (mycobacteria plus various adjuvant-active oils), (2) collagen type-II with Freund's incomplete adjuvant (no mycobacteria), (3) the synthetic lipid amine, avridine in an oil and (4) the natural hydrocarbons squalene (C 30H50) and pristane (C19H40). This pro-arthritic effect was independent of sex, rat strain or changing diet and housing facilities. Thiocyanate supplements also amplified the acute/persisting inflammatory responses to paw injections of pristane, zymosan and microcrystalline hydroxyapatite. Iodide salts also mimicked some of these effects of thiocyanate. Conclusion: Thiocyanate, a detoxication product of HCN present in tobacco smoke, increased (or even induced) inflammatory responses to several agents causing arthritis or fibrotic inflammation in rats. It, therefore, can act as a co-arthritigen, or 'virulence factor' and could be a therapeutic target to reduce arthritis expression and morbidity.
AB - Objective: To seek a mechanism linking tobacco smoking with the increased incidence and severity of rheumatoid arthritis, deduced from many retrospective surveys, by studying arthritis/fibrosis development in rats. Methods: Rats (>300) received low levels of sodium/potassium thiocyanate (10 or 25 mmol/l) in their drinking water to raise their blood thiocyanate levels, mimicking the elevated levels of blood, salivary and urinary thiocyanate found in smokers. Results: Thiocyanate supplements increased the severity of experimental arthritis induced by tailbase injection of (1) Freund's complete adjuvants (mycobacteria plus various adjuvant-active oils), (2) collagen type-II with Freund's incomplete adjuvant (no mycobacteria), (3) the synthetic lipid amine, avridine in an oil and (4) the natural hydrocarbons squalene (C 30H50) and pristane (C19H40). This pro-arthritic effect was independent of sex, rat strain or changing diet and housing facilities. Thiocyanate supplements also amplified the acute/persisting inflammatory responses to paw injections of pristane, zymosan and microcrystalline hydroxyapatite. Iodide salts also mimicked some of these effects of thiocyanate. Conclusion: Thiocyanate, a detoxication product of HCN present in tobacco smoke, increased (or even induced) inflammatory responses to several agents causing arthritis or fibrotic inflammation in rats. It, therefore, can act as a co-arthritigen, or 'virulence factor' and could be a therapeutic target to reduce arthritis expression and morbidity.
UR - http://www.scopus.com/inward/record.url?scp=70349278461&partnerID=8YFLogxK
U2 - 10.1007/s00011-009-0038-2
DO - 10.1007/s00011-009-0038-2
M3 - Article
C2 - 19360377
AN - SCOPUS:70349278461
SN - 1023-3830
VL - 58
SP - 693
EP - 704
JO - Inflammation Research
JF - Inflammation Research
IS - 10
ER -