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Treatment with interferon-alpha (IFNα) of hepatitis C patients induces lower serum dipeptidyl peptidase IV activity, which is related to IFNα-induced depressive and anxiety symptoms and immune activation

Molecular Psychiatry volume 6, pages 475–480 (2001)Cite this article

Abstract

We have shown that treatment with interleukin-2 (IL-2) or interferon-α (IFNα) may induce depressive symptoms and activation of the cytokine network and that IL-2 treatment may diminish serum dipeptidyl pepdidase IV (DPP IV) activity.1–3 DPP IV (EC 3.4.14.5) is a membrane bound serine protease which catalyzes the cleavage of some cytokines and neuroactive peptides which modulate T cell activity.4 The aims of the present study were to examine the effects of IFNα-based immunotherapy on serum DPP IV activity in relation to induction of the inflammatory response system. In 18 patients with chronic active hepatitis C, we determined the Montgomery and Asberg Rating Scale (MADRS),5 the Hamilton Anxiety Rating Scale (HAM-A),6 serum DPP IV activity, the kynurenine/tryptophan (K/T) quotient, which is an indicator of cytokine (in particular IFN)-induced catabolism of tryptophan,7 and serum interleukin-8 (IL-8) before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFNα. IFNα-immunotherapy significantly suppressed serum DPP IV 2–4 weeks and 16–24 weeks after starting IFNα-based immunotherapy. The reduction in serum DPP IV activity was more pronounced 16–24 weeks after starting immunotherapy than after 2–4 weeks. The IFNα-induced suppression of serum DPP IV activity was significantly correlated to IFNα-induced increases in the MADRS and HAM-A and increases in the K/T quotient and serum IL-8. In conclusion, long-term immunotherapy with IFNα suppresses serum DPP IV activity and the immunotherapy-induced changes in DPP IV are related to increases in severity of depression, anxiety and activation of the inflammatory response system.

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Acknowledgements

This work was supported by a grant from the National Council for Research No. 203.04.17 of 09/06/97. We would like to thank Professor Dr S Scharpe, Dr I DeMeester and C Durinx for their valuable help.

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Authors and Affiliations

  1. Department of Psychiatry, University Hospital of Maastricht, Maastricht, The Netherlands

    M Maes & S Bonaccorso

  2. Department of Psychiatry, Vanderbilt University, Nashville, USA

    M Maes, S Bonaccorso & H Meltzer

  3. Psychiatric Hospital, University ‘La Sapienza’, Rome, Italy

    S Bonaccorso, V Marino, A Puzella, M Pasquini & M Biondi

  4. Department of Hepatology, I Medical Clinic, University ‘La Sapienza’, Rome, Italy

    M Artini & C Almerighi

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Correspondence to M Maes.

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Maes, M., Bonaccorso, S., Marino, V. et al. Treatment with interferon-alpha (IFNα) of hepatitis C patients induces lower serum dipeptidyl peptidase IV activity, which is related to IFNα-induced depressive and anxiety symptoms and immune activation. Mol Psychiatry 6, 475–480 (2001). https://doi.org/10.1038/sj.mp.4000872

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