The monocyte-derived cytokine, tumor necrosis factor α (TNFα), is essential for host immunity, but overproduction of this cytokine may have serious pathologic consequences. Excess TNFα produced in pulmonary tuberculosis may cause fevers, weakness, night sweats, necrosis, and progressive weight loss. Thalidomide (α-N-phthalimidoglutarimide) has recently been shown to suppress TNFα production by human monocytes in vitro and to reduce serum TNFα in leprosy patients. We have therefore conducted a two-part placebo-controlled pilot study of thalidomide in patients with active tuberculosis to determine its effects on clinical response, immune reactivity, TNFα levels, and weight.

30 male patients with active tuberculosis, either human immunodeficiency virus type 1 positive (HIV-1⁺) or HIV-1⁻, received thalidomide or placebo for single or multiple 14 day cycles. Toxicity of the study drug, delayed type hypersensitivity (DTH), cytokine production, and weight gain were evaluated.

Thalidomide treatment was well tolerated, without serious adverse events. The drug did not adversely affect the DTH response to purified protein derivative (PPD), total leukocyte, or differential cell counts. TNFα production was significantly reduced during thalidomide treatment while interferon-γ (IFNγ) production was enhanced. Daily administration of thalidomide resulted in a significant enhancement of weight gain.

The results indicate that thalidomide is well tolerated by patients receiving anti-tuberculosis therapy. Thalidomide treatment reduces TNFα production both in vivo and in vitro and is associated with an accelerated weight gain during the study period.