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.