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Thalidomide Treatment Reduces Tumor Necrosis Factor α Production and Enhances Weight Gain in Patients with Pulmonary Tuberculosis

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Abstract

Background

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.

Materials and Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

We thank the nurses Sumalee Ammarinsangpen, Jinda Tongsuradet and Amporn Suwanprasert, from the Chiang Mai tuberculosis control center, for making this study possible. Dr. Attapon Cheepsatayakorn is acknowledged for help with the radiology. We also thank Cynthia Seidman, Dacia Vasquez, and Jolanta Diakun from the Dietary Service at the Rockefeller University GCRC, and the nurses and staff of the Rockefeller University Hospital; Marguerite Nulty for typing the manuscript; Judy Adams for help with the figures; and Jason Tian for help with the statistical analysis. Dr. Victoria Schauf helped initiate these studies. Dr. Victoria Freedman’s help in writing the manuscript is gratefully acknowledged. This study was supported in part by U.S. Public Health Service Grants AI 24775, AI 33124, and AI 07012, a Rockefeller University General Clinical Research Center Grant (MO1-RR00102), Grunenthal GMBH, and Celgene Corporation.

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Authors and Affiliations

  1. Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Avenue, New York, New York, 10021, USA

    Jane M. Tramontana, Utaiwan Utaipat, Anthony Molloy, Margaret Burroughs, Barbara Johnson & Gilla Kaplan

  2. Department Microbiology and Faculty Medicine, Chiang Mai University, Chiang Mai, Thailand

    Utaiwan Utaipat & Sanit Makonkawkeyoon

  3. Chiang Mai Anti-TB Association, Chiang Mai, Thailand

    Pasakorn Akarasewi

  4. Department Medicine and Pulmonary and Critical Care Medicine, New York University Medical Center, 550 First Avenue, New York, New York, USA

    Jeffrey D. Klausner & William Rom

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  1. Jane M. Tramontana
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  2. Utaiwan Utaipat
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  3. Anthony Molloy
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  4. Pasakorn Akarasewi
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  5. Margaret Burroughs
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  6. Sanit Makonkawkeyoon
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  7. Barbara Johnson
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  8. Jeffrey D. Klausner
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  9. William Rom
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  10. Gilla Kaplan
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Tramontana, J.M., Utaipat, U., Molloy, A. et al. Thalidomide Treatment Reduces Tumor Necrosis Factor α Production and Enhances Weight Gain in Patients with Pulmonary Tuberculosis. Mol Med 1, 384–397 (1995). https://doi.org/10.1007/BF03401576

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  • DOI: https://doi.org/10.1007/BF03401576

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