Host and Environmental Factors Influencing Individual Human Cytokine Responses

Rob ter Horst, Martin Jaeger, Sanne P. Smeekens, Marije Oosting, Morris A. Swertz, Yang Li, Vinod Kumar, Dimitri A. Diavatopoulos, Anne F.M. Jansen, Heidi Lemmers, Helga Toenhake-Dijkstra, Antonius E. van Herwaarden, Matthijs Janssen, Renate G. van der Molen, Irma Joosten, Fred C.G.J. Sweep, Johannes W. Smit, Romana T. Netea-Maier, Mieke M.J.F. Koenders, Ramnik J. XavierJos W.M. van der Meer, Charles A. Dinarello, Norman Pavelka, Cisca Wijmenga, Richard A. Notebaart, Leo A.B. Joosten*, Mihai G. Netea

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

239 Citations (Scopus)


Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project, we assessed the effect of environmental and non-genetic host factors of the genetic make-up of the host and of the intestinal microbiome on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral, and non-microbial metabolic stimuli in 534 healthy subjects. In this first study, we show a strong impact of non-genetic host factors (e.g., age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies. PaperClip

Original languageEnglish
Pages (from-to)1111-1124.e13
Issue number4
Publication statusPublished - 3 Nov 2016
Externally publishedYes


  • age
  • alpha-1-antitrypsin
  • cytokines
  • environment
  • gender
  • genetics
  • host
  • microbiome
  • season
  • vitamin D


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