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Antimicrobial Agents and Chemotherapy, September 2000, p. 2286-2290, Vol. 44, No. 9
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Single Oral Dose of Thalidomide Enhances the Capacity of Lymphocytes to Secrete Gamma Interferon in Healthy Humans

Annelies Verbon,1,* Nicole P. Juffermans,1,2 Peter Speelman,1 Sander J. H. van Deventer,2 Ineke J. M. ten Berge,3 Henk-Jan Guchelaar,4 and Tom van der Poll1,2

Department of Infectious Diseases, Tropical Medicine and AIDS,1 Laboratory of Experimental Internal Medicine,2 Clinical Immunology Laboratory,3 and Department of Clinical Pharmacy,4 Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Received 3 February 2000/Returned for modification 31 March 2000/Accepted 31 May 2000

Thalidomide is increasingly being used as adjuvant therapy for patients with mycobacterial and human immunodeficiency virus (HIV) infections. The T-helper (Th)1 cytokine-Th2 cytokine balance critically determines the outcomes of these diseases. To obtain insight into the effect of thalidomide on the capacity of lymphocytes to produce Th1 and Th2 cytokines, six healthy volunteers received an oral dose (400 mg) of thalidomide. Before and at 3, 6, and 24 h after ingestion of thalidomide, peripheral blood mononuclear cells (PBMCs) were isolated and stimulated for 24 h with the T-cell stimulant staphylococcal enterotoxin B (SEB) or anti-CD3/CD28. In all six volunteers ingestion of thalidomide was associated with enhanced SEB- and anti-CD3/CD28-induced production of the Th1 cytokine gamma interferon (P < 0.05) and a decrease in the level of anti-CD3/CD28-induced interleukin-5 (IL-5) production (P < 0.05). The levels of IL-2 (Th1) and IL-4 (Th2) released remained unchanged. These changes were accompanied by an increase in the amount of IL-12p40 released by the PBMCs 6 h after ingestion of thalidomide (P < 0.05). Thus, a single oral dose of thalidomide causes a Th1-type response in healthy humans. This finding offers a potential explanation for the positive effect of thalidomide in patients with mycobacterial and HIV infections.

* Corresponding author. Mailing address: Department of Infectious Diseases, Tropical Medicine and AIDS, F4-222, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Phone: 31-20-5669111. Fax: 31-20-6972286. E-mail: A.verbon{at}amc.uva.nl.

Antimicrobial Agents and Chemotherapy, September 2000, p. 2286-2290, Vol. 44, No. 9
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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