Open Access

ARTICLE

Cytokine production from stimulated whole blood cultures in rheumatoid arthritis patients treated with various TNF blocking agents

Calin Popa^1,2, Pilar Barrera², Leo A. B. Joosten^1,2,3, Piet L. C. M. van Riel², Bart-Jan Kullberg^1,3, Jos W. M. van der Meer^1,3, Mihai G. Netea^1,3

1 Department of General Internal Medicine
2 Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
3 Nijmegen Institute for Infection, Inflammation, and Immunity (N4i), Radboud University Nijmegen, Nijmegen, The Netherlands

* Corresponding Author: C. Popa,

European Cytokine Network 2009, 20(2), 88-83. https://doi.org/10.1684/ecn.2009.0150

Accepted 10 April 2009;

Abstract

Infectious complications are not rare in rheumatoid arthritis (RA), and the susceptibility to infec-tions is increased during treatment with TNF blocking agents. As a possible mechanism contributing to that, we assessed the modulation of cytokine production induced by TNF neutralization. Methods. Whole blood cultures from six healthy volunteers and 13 RA patients starting therapy with either adalimumab (n = 7) or etanercept (n = 6) were stimulated with heat-killed Salmonella typhimurium, Staphylococcus aureus or with S. typhimurium lipopolysaccharide (LPS). The production of interleukin (IL)-1β, IL-6, IL10, IL-17, TNF, IL-8 and IFN-γ was measured by specific immunoassays. Results. Stimulation with Salmonella LPS resulted in a significantly lower production of IL-1β, TNF and a trend towards lower IL-6 and IFN-γ production in RA patients compared to healthy volunteers. Therapy with either of the agents did not significantly alter cytokine production capacity, with the exception of a lower IFN-γ and IL-8 production in patients treated with adalimumab and stimulated with heat-killed S. aureus. Conclusion. The results of our study suggest that the detrimental effects of anti-TNF agents on the immune response can vary quite widely, from very serious to limited effects, as reported here for etanercept and adalimumab. Because anti-TNF therapy can affect the cellular integrity of tuberculous granu-loma, recruitment of new cells at the granuloma site becomes crucial. In line with this, an impaired chemokine production induced by anti-TNF agents may ultimately result in the reactivation of tuberculosis, as previously reported. Therefore, caution should be constantly exercised in order to prevent the development of severe infec-tions and reactivation of tuberculosis whenever therapy with anti-TNF is initiated.

---

Keywords

anti-TNF therapy, rheumatoid arthritis, infections, immune response

---

Cite This Article

APA Style

Popa, C., Barrera, P., Joosten, L.A.B., Riel, P.L.C.M.V., Kullberg, B. et al. (2009). Cytokine production from stimulated whole blood cultures in rheumatoid arthritis patients treated with various TNF blocking agents. European Cytokine Network, 20(2), 88–83. https://doi.org/10.1684/ecn.2009.0150

Vancouver Style

Popa C, Barrera P, Joosten LAB, Riel PLCMV, Kullberg B, Meer JWMVD, et al. Cytokine production from stimulated whole blood cultures in rheumatoid arthritis patients treated with various TNF blocking agents. Eur Cytokine Network. 2009;20(2):88–83. https://doi.org/10.1684/ecn.2009.0150

IEEE Style

C. Popa et al., “Cytokine production from stimulated whole blood cultures in rheumatoid arthritis patients treated with various TNF blocking agents,” Eur. Cytokine Network, vol. 20, no. 2, pp. 88–83, 2009. https://doi.org/10.1684/ecn.2009.0150

BibTex EndNote RIS