       Document 0174
 DOCN  M9630174
 TI    Thalidomide treatment reduces tumor necrosis factor alpha production and
       enhances weight gain in patients with pulmonary tuberculosis.
 DT    9603
 AU    Tramontana JM; Utaipat U; Molloy A; Akarasewi P; Burroughs M;
       Makonkawkeyoon S; Johnson B; Klausner JD; Rom W; Kaplan G; Laboratory of
       Cellular Physiology and Immunology, Rockefeller; University, New York,
       NY 10021, USA.
 SO    Mol Med. 1995 May;1(4):384-97. Unique Identifier : AIDSLINE MED/96091362
 AB    BACKGROUND: The monocyte-derived cytokine, tumor necrosis factor alpha
       (TNF alpha), is essential for host immunity, but overproduction of this
       cytokine may have serious pathologic consequences. Excess TNF alpha
       produced in pulmonary tuberculosis may cause fevers, weakness, night
       sweats, necrosis, and progressive weight loss. Thalidomide
       (alpha-N-phthalimidoglutarimide) has recently been shown to suppress TNF
       alpha production by human monocytes in vitro and to reduce serum TNF
       alpha 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, TNF alpha 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. TNF alpha production was significantly reduced
       during thalidomide treatment while interferon-gamma (IFN gamma)
       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 TNF alpha
       production both in vivo and in vitro and is associated with an
       accelerated weight gain during the study period.
 DE    Adult  Aged  Cells, Cultured  Cytokines/BIOSYNTHESIS  Human
       Hypersensitivity, Delayed/CHEMICALLY INDUCED  Immunosuppressive
       Agents/ADVERSE EFFECTS/*THERAPEUTIC USE  Leukocytes,
       Mononuclear/METABOLISM  Male  Middle Age  Pilot Projects  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Thalidomide/ADVERSE
       EFFECTS/*THERAPEUTIC USE  Tuberculosis, Pulmonary/*DRUG
       THERAPY/METABOLISM/PHYSIOPATHOLOGY  Tumor Necrosis Factor/ANTAGONISTS &
       INHIB/*BIOSYNTHESIS  Weight Gain/DRUG EFFECTS  CLINICAL TRIAL  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

