Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inhaled from tobacco smoke.
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(30)H(50)) and pristane (C(19)H(40)). 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.


CONCLUSIONS
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.
Whitehouse
Michael Wellesley
MW
Department of Pathology, University of Adelaide, Adelaide, SA, 5005, Australia. whitehousemd@spin.net.au
Jones
Mark
M
D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000382:microbiology; D003094:Collagen / Q000009:adverse effects; D003959:Diamines / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D006838:Hydrocarbons / Q000009:adverse effects; D006856:Hydrogen Cyanide / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D009161:Mycobacterium; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects*; D013861:Thiocyanates / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*
D003959:Diamines; D006838:Hydrocarbons; D013861:Thiocyanates; D006856:Hydrogen Cyanide; C024553:sodium thiocyanate; D003094:Collagen; C031760:thiocyanate; C006270:avridine; C009941:potassium thiocyanate