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Polymorphisms in cytokine genes IL6, TNF, IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections

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Abstract

Complicated skin and skin structure infections (cSSSIs) are caused by Gram-positive and Gram-negative, aerobic and anaerobic pathogens, with a polymicrobial aetiology being frequent. Recognition of invading pathogens by the immune system results in the production of pro- and anti-inflammatory cytokines, which are extremely important for intercellular communication and control of infection. This study assessed whether genetic variation in genes encoding cytokines influences the susceptibility to cSSSIs. For the association study, 318 patients with cSSSI and 328 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) in cytokine genes IL1A, IL1B, IL1RN, TNF, IL10, IL17A, IL17F and IFNG. For immunological validation, peripheral blood mononuclear cells (PBMCs) from 74 healthy individuals, genotyped for SNPs of interest, were stimulated with Staphylococcus aureus or Escherichia coli and corresponding cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). Polymorphisms IL6 rs1800797, TNF rs1800629, IL10 rs1800871, IL17A rs8193036 and IFNG rs2069705 influenced susceptibility to cSSSIs. No differences in cytokine responses, stratified for genotype, were detected after PBMC stimulation. No association with cSSSIs was observed for polymorphisms IL1A rs17561 and rs1800587, IL1B rs16944 and rs1143627, IL1RN rs4251961, TNF rs361525, IL10 rs1800896, IL17A rs2275913 and IL17F rs763780. In conclusion, polymorphisms in IL6, TNF, IL10, IL17A and IFNG are associated with susceptibility to cSSSIs.

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Acknowledgements

We are grateful to all the patients, investigators and study centres who participated in the RELIEF clinical trial. Special thanks go to Johanna Beekman (Bayer Healthcare, Berlin, Germany) for the collection, preparation and storage of patient blood samples for genotypic analysis. Liesbeth Bruckers (CenStat, Hasselt University, Hasselt, Belgium) is acknowledged for the assistance with the statistical analysis.

Conflict of interest

This work was supported by an unrestricted grant from Bayer Healthcare. P.R. is an employee of Bayer Healthcare. T.S.P. was supported by a Veni grant of the Netherlands Organization for Scientific Research. M.G.N. was supported by a European Research Council Consolidator Grant 310372.

Author information

Authors and Affiliations

  1. Department of Internal Medicine (463), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands

    M. H. T. Stappers, Y. Thys, M. Oosting, T. S. Plantinga, M. Ioana, M. G. Netea, L. A. B. Joosten & I. C. Gyssens

  2. Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands

    J. W. Mouton

  3. Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

    M. H. T. Stappers, J. W. Mouton & I. C. Gyssens

  4. Hasselt University, Hasselt, Belgium

    M. H. T. Stappers, Y. Thys & I. C. Gyssens

  5. Bayer Healthcare Pharmaceuticals, Wuppertal, Germany

    P. Reimnitz

  6. Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands

    J. W. Mouton

Authors
  1. M. H. T. Stappers
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  2. Y. Thys
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  3. M. Oosting
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  4. T. S. Plantinga
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  5. M. Ioana
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  6. P. Reimnitz
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  7. J. W. Mouton
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  8. M. G. Netea
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  9. L. A. B. Joosten
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  10. I. C. Gyssens
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Corresponding author

Correspondence to I. C. Gyssens.

Additional information

Leo A.B. Joosten and Inge C. Gyssens share senior authorship.

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Stappers, M.H.T., Thys, Y., Oosting, M. et al. Polymorphisms in cytokine genes IL6, TNF, IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections. Eur J Clin Microbiol Infect Dis 33, 2267–2274 (2014). https://doi.org/10.1007/s10096-014-2201-0

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  • DOI: https://doi.org/10.1007/s10096-014-2201-0

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