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Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inhaled from tobacco smoke

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Abstract

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 (C30H50) 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.

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Acknowledgments

We are much indebted to Professor G. Graham (Sydney) for helpful discussions, to Professors B. Vernon-Roberts (Adelaide), M.S. Roberts (Brisbane) and G.R. Bushell (Brisbane) for providing animal facilities, to L. Chan and G. Koerbin (Brisbane) for plasma thiocyanate analyses, D.E. Butters for preparing the typescript, and two reviewers for incisive comments. Financial support was provided successively by the National Health & Medical Research Council, Canberra; Pharma Quest, Coorparoo, Queensland, and private resources.

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Authors and Affiliations

  1. Department of Pathology, University of Adelaide, Adelaide, SA, 5005, Australia

    Michael Wellesley Whitehouse

  2. Therapeutics Research Unit, Department of Medicine, University of Queensland, Brisbane, QLD, Australia

    Michael Wellesley Whitehouse

  3. School of Biomolecular and Physical Sciences, Griffith University, Nathan, QLD, 4111, Australia

    Michael Wellesley Whitehouse

  4. Queensland Clinical Trials Centre, School of Population Health, University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD, 4102, Australia

    Mark Jones

  5. PO Box 68, Stones Corner, QLD, 4120, Australia

    Michael Wellesley Whitehouse

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Correspondence to Michael Wellesley Whitehouse.

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Responsible Editor: M. J. Parnham.

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Whitehouse, M.W., Jones, M. Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inhaled from tobacco smoke. Inflamm. Res. 58, 693–704 (2009). https://doi.org/10.1007/s00011-009-0038-2

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  • DOI: https://doi.org/10.1007/s00011-009-0038-2

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