THALIDOMIDE TREATMENT REDUCES TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION AND ENHANCES WEIGHT-GAIN IN PATIENTS WITH PULMONARY TUBERCULOSIS

Background: The monocyte-derived cytokine, tu:mor necrosis factor alph a (TNF alpha), is essential for host immunity, but overproduction of t his cytokine may have serious pathologic consequences. Excess TNF alph a produced in pulmonary tuberculosis may cause fevers, weakness, night sweats, necrosis, and progressive weight loss. Thalidomide (alpha-N-p hthalimidoglutarimide) has recently been shown to suppress TNF alpha p roduction by human monocytes in vitro and to reduce serum TNF alpha in leprosy patients. We have therefore conducted a two-part placebo-cont rolled pilot study of thalidomide in patients with active tuberculosis to determine its effects on clinical response, immune reactivity, TNF alpha levels, and weight. Materials and Methods: 30 male patients wit h active tuberculosis, either human immunodeficiency virus type 1 posi tive (HIV-1(+)) or HIV-1(-), received thalidomide or placebo for singl e or multiple 14 day cycles. Toxicity of the study drug, delayed type hypersensitivity (DTH), cytokine production, and weight gain were eval uated. Results: Thalidomide treatment was well tolerated, without seri ous adverse events. The drug did not adversely affect the DTH response to purified protein derivative (PPD), total leukocyte, or differentia l cell counts. TNF alpha production was significantly reduced during t halidomide treatment while interferon-gamma (IFN gamma) production was enhanced. Daily administration of thalidomide resulted in a significa nt enhancement of weight gain. Conclusions: The results indicate that thalidomide is well tolerated by patients receiving anti-tuberculosis therapy. Thalidomide treatment reduces TNF alpha production both in vi vo and in vitro and is associated with an accelerated weight gain duri ng the study period.