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Azithromycin in combination with riboflavin decreases the severity of Staphylococcus aureus infection induced septic arthritis by modulating the production of free radicals and endogenous cytokines

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Abstract

Objective and design

To determine alternate therapeutic measures to combat Staphylococcus aureus induced arthritis. Thus, azithromycin was combined with riboflavin, which may combat the ROS production and inflammation.

Methods

An in vivo model of S. aureus infection-induced arthritis was set up by infecting mice with 5 × 106 bacterial cell/mouse. S. aureus was administered intravenously. Azithromycin and riboflavin was injected intraperitoneally at a single dose of 100 and 20 mg/kg body, respectively. The mice were sacrificed at 3, 9, 15 days post infection (dpi). TNF-α, IFN-γ, IL-6 and IL-10 from serum and SOD, catalase and reduced glutathione concentration were observed in hepatic, cardiac, renal and splenic tissue.

Results

CFU was found very prominent in spleen and joints and reduced in blood at 3 and 9 dpi. However, treatment with azithromycin and riboflavin completely eradicated the bacteria from blood and spleen. TNF-α, IFN-γ, IL-6, and MCP-1 were induced due to infection which were downregulated by treatment with azithromycin and riboflavin. Infected mice were also found to have altered antioxidant status, measured in terms of reduced glutathione and anti-oxidant enzymes such as SOD and catalase.

Conclusion

These changes were found to be ameliorated when the animals were co-treated with azithromycin and riboflavin.

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Acknowledgments

The corresponding author (Biswadev Bishayi) thanks the Council of Scientific and Industrial Research (CSIR) Ministry of Human Resource Development, Government of India, New Delhi, India for funding this project. The author (BB) is indebted to Dr. Sunil Kumar Manna, Scientist and Head, Immunology Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India for providing us with the primers for TSST-1 and coagulase. KD is recipient of Research Associateship in Biotechnology and Life Sciences from Department of Biotechnology, Govt. of India.

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Authors and Affiliations

  1. Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta, 700009, West Bengal, India

    Pinky Mal, Rajni Khan & Biswadev Bishayi

  2. National Brain Research Centre, Manesar, Haryana, 122051, India

    Kallol Dutta & Anirban Basu

  3. Department of Physiology, Oxidative Stress and Free Radical Biology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta, 700009, West Bengal, India

    Debasish Bandyopadhyay

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  1. Pinky Mal
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  2. Kallol Dutta
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  3. Debasish Bandyopadhyay
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Correspondence to Biswadev Bishayi.

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Responsible Editor: John Di Battista.

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Mal, P., Dutta, K., Bandyopadhyay, D. et al. Azithromycin in combination with riboflavin decreases the severity of Staphylococcus aureus infection induced septic arthritis by modulating the production of free radicals and endogenous cytokines. Inflamm. Res. 62, 259–273 (2013). https://doi.org/10.1007/s00011-012-0574-z

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  • DOI: https://doi.org/10.1007/s00011-012-0574-z

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