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Research Article

Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity

  • Alyson A. Kelvin mail,

    akelvin@sardiniaresearchanddevelopment.com

    Affiliations: Sardinia Research and Development (SaRD), University di Sassari, Sassari, Italy, Immune Diagnostics and Research (IDR), Toronto Medical Discovery Tower (TDMT), Toronto, Ontario, Canada

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  • David Banner,

    Affiliation: Experimental Therapeutics, University Health Network (UHN), Toronto, Ontario, Canada

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  • Giuliano Silvi,

    Affiliation: Dipartimento di Sanità Pubblica, Azienda Usl di Ravenna, Ferrara, Italy

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  • Maria Luisa Moro,

    Affiliation: Agenzia Sanitaria e Sociale Regione Emilia-Romagna, Bologna, Italy

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  • Nadir Spataro,

    Affiliation: Department of Hematology and Oncology, Alma Mater Studiorum - University of Bologna, Bologna, Italy

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  • Paolo Gaibani,

    Affiliation: Department of Hematology and Oncology, Alma Mater Studiorum - University of Bologna, Bologna, Italy

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  • Francesca Cavrini,

    Affiliation: Department of Hematology and Oncology, Alma Mater Studiorum - University of Bologna, Bologna, Italy

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  • Anna Pierro,

    Affiliation: Department of Hematology and Oncology, Alma Mater Studiorum - University of Bologna, Bologna, Italy

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  • Giada Rossini,

    Affiliation: Department of Hematology and Oncology, Alma Mater Studiorum - University of Bologna, Bologna, Italy

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  • Mark J. Cameron,

    Affiliation: Experimental Therapeutics, University Health Network (UHN), Toronto, Ontario, Canada

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  • Jesus F. Bermejo-Martin,

    Affiliations: National Centre of Influenza, Hospital Clínico Universitario de Valladolid, Valladolid, Spain, Unidad de Investigación en Infección e Inmunidad - Microbiology Service, Hospital Clínico Universitario de Valladolid - Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL), Valladolid, Spain

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  • Stéphane G. Paquette,

    Affiliations: Experimental Therapeutics, University Health Network (UHN), Toronto, Ontario, Canada, Faculty of Medicine, Institute of Medical Science (IMS), University of Toronto, Toronto, Ontario, Canada

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  • Luoling Xu,

    Affiliation: Experimental Therapeutics, University Health Network (UHN), Toronto, Ontario, Canada

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  • Ali Danesh,

    Affiliation: Experimental Therapeutics, University Health Network (UHN), Toronto, Ontario, Canada

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  • Amber Farooqui,

    Affiliation: Sardinia Research and Development (SaRD), University di Sassari, Sassari, Italy

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  • Ilaria Borghetto,

    Affiliations: Sardinia Research and Development (SaRD), University di Sassari, Sassari, Italy, Dipartimento di Scienze Biomediche, University di Sassari, Sassari, Italy

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  • David J. Kelvin,

    Affiliations: Experimental Therapeutics, University Health Network (UHN), Toronto, Ontario, Canada, Faculty of Medicine, Institute of Medical Science (IMS), University of Toronto, Toronto, Ontario, Canada, PhD School in Biomolecular and Biotechnology Sciences, University of Sassari, Sassari, Italy

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  • Vittorio Sambri,

    Affiliation: Department of Hematology and Oncology, Alma Mater Studiorum - University of Bologna, Bologna, Italy

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  • Salvatore Rubino

    Affiliations: Sardinia Research and Development (SaRD), University di Sassari, Sassari, Italy, Dipartimento di Scienze Biomediche, University di Sassari, Sassari, Italy

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  • Published: August 16, 2011
  • DOI: 10.1371/journal.pntd.0001279

Reader Comments (1)

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Previous study & Fig.4.

Posted by Olaf_Rotzschke on 01 Sep 2011 at 05:26 GMT

Dear colleagues,

I appreciate your work on chicungunya infection. It is in fact one of the emerging diseases that clearly deserves more attention in the field. I like to make to comments though:

Firstly, I want to point out that a prior study with almost identical design has been published early this year (Chow et al., J Infect Dis. 2011 Jan 15;203(2):149-57). The study produced in part very similar results but had not been mentioned in this paper.

Secondly, I'm having some problem in interpreting Fig. 4. Serum levels of IL-2 and IL-4 are usually so low that they are very hard to detect by luminex (evident also in the very low median < 5pg/ml for healthy control; see PLoS ONE 3(7): e2535). Thus, to conclude from the absence of any positive signal that they are not associated with the viral infection just appears to me not substantiated by the data.
Even more confusing is the statement regarding the role of IL-8 in this context. In contrast, to IL-2 and IL-4 this chemokine can be easily detected in all the patients. In fact, in Fig. 4 the values of IL8 for all patient groups are clearly way above the dotted line representing the median of the healthy control. So, does the line really reflect the median control and, if this is the case, why is IL-8 then declared not to be associated with infection??

Curious on your reply!

No competing interests declared.

RE: Previous study & Fig.4.

AKelvin replied to Olaf_Rotzschke on 01 Sep 2011 at 14:30 GMT

Dear Dr. Rotzschke,

Thank you very much for your comments. They are very much appreciated.

I agree that the Chow study is very excellent and perhaps should have been included. The reason it was not included was that the paper was in the final stages of revisions at the time of the Chow publication.

As for your interest in Fig 4. Our experiments were not run by Illuminex but by CBA. It is true that the values are low but the conclusion is that the data does not support a role in resolution. It is possible that further investigation may a potential role but here there was not a statistical trend seen in relation to resolution. It is mentioned that the values are statistically different that the control group. Perhaps a conclusion can be made in light of these statistical differences but in this report, the conclusion were based on the significant trends.

Thank you again for your comments. Please contact me further with any other questions or discussions.

Sincerely,

Alyson Kelvin

No competing interests declared.