Abstract
Thalidomide selectively inhibits the production of human monocyte tumor necrosis factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide and other agonists in culture. 40% inhibition occurs at the clinically achievable dose of the drug of 1 micrograms/ml. In contrast, the amount of total protein and individual proteins labeled with [35S]methionine and expressed on SDS-PAGE are not influenced. The amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony-stimulating factor produced by monocytes remain unaltered. The selectivity of this drug may be useful in determining the role of TNF-alpha in vivo and modulating its toxic effects in a clinical setting.
MeSH Terms
Blood Proteins/biosynthesis,isolation & purification
Cytokines/biosynthesis,blood
Endotoxins/pharmacology
Humans
In Vitro Techniques
Kinetics
Lipopolysaccharides/pharmacology
Molecular Weight
Monocytes/drug effects,physiology
Salmonella
Thalidomide/pharmacology
Tumor Necrosis Factor-alpha/biosynthesis
Chemicals
Blood Proteins
Cytokines
Endotoxins
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Thalidomide
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sampaio E P
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
Sarno E N
Galilly R
Cohn Z A
Kaplan G
References (20)
20 references, click to expand
-
Reactions in leprosy.
Lepr Rev. 1969 Apr;40(2):77-81
PMID: 5792378
-
The saga of thalidomide. Neuropathy to embryopathy, with case reports of congenital anomalies.
N Engl J Med. 1962 Dec 6;267:1184-92 contd
PMID: 13934699
-
Measurement of cell numbers by means of the endogenous enzyme hexosaminidase. Applications to detection of lymphokines and cell surface antigens.
J Immunol Methods. 1984 Mar 16;67(2):379-88
PMID: 6200537
-
Thalidomide--effect on T cell subsets as a possible mechanism of action.
Int J Lepr Other Mycobact Dis. 1985 Jun;53(2):201-5
PMID: 3874920
-
Direct stimulation of monocyte release of interleukin 1 by mycobacterial protein antigens.
J Immunol. 1986 Jan;136(1):193-6
PMID: 3484390
-
Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance.
Science. 1986 May 23;232(4753):977-80
PMID: 3754653
-
Raised serum levels of tumour necrosis factor in parasitic infections.
Lancet. 1986 Dec 13;2(8520):1364-5
PMID: 2878227
-
Suppression of in vivo polyclonal IgE responses by monoclonal antibody to the lymphokine B-cell stimulatory factor 1.
Proc Natl Acad Sci U S A. 1986 Dec;83(24):9675-8
PMID: 3491987
-
Tumors secreting human TNF/cachectin induce cachexia in mice.
Cell. 1987 Aug 14;50(4):555-63
PMID: 3607879
-
Evidence for tumour necrosis factor/cachectin production in cancer.
Lancet. 1987 Nov 28;2(8570):1229-32
PMID: 2890853
-
Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation.
J Exp Med. 1988 Mar 1;167(3):1211-27
PMID: 3351436
-
Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura.
N Engl J Med. 1988 Aug 18;319(7):397-400
PMID: 3135497
-
Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome.
Am J Med. 1988 Sep;85(3):289-91
PMID: 3414726
-
Acylation of monocyte and glomerular mesangial cell proteins. Myristyl acylation of the interleukin 1 precursors.
J Clin Invest. 1988 Nov;82(5):1479-88
PMID: 3263392
-
The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome.
J Exp Med. 1989 Jan 1;169(1):333-8
PMID: 2783334
-
Regulation of the expression of IL-6 in human monocytes.
J Immunol. 1989 Jun 15;142(12):4339-45
PMID: 2786029
-
Evidence that tumor necrosis factor has an important role in antibacterial resistance.
J Immunol. 1989 Nov 1;143(9):2894-9
PMID: 2509559
-
Induction of interleukin 1 and tumor necrosis factor by mycobacterial proteins: the monocyte western blot.
Proc Natl Acad Sci U S A. 1990 May;87(9):3348-52
PMID: 2110362
-
Local production of tumor necrosis factor and IFN-gamma in tuberculous pleuritis.
J Immunol. 1990 Jul 1;145(1):149-54
PMID: 2113553
-
Thalidomide: use and possible mode of action in reactional lepromatous leprosy and in various other conditions.
J Am Acad Dermatol. 1982 Sep;7(3):317-23
PMID: 7130490