Somnogenic,
pyrogenic, and anorectic activities of tumor necrosis factor-a
and TNF-a
fragments
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Kapás L,
Hong L, Cady AB, Opp MR, Postlethwaite AE, Seyer JM, Krueger JM
Department of Physiology
and Biophysics, University of Tennessee, Memphis, TN
Am. J. Physiol.
1992 263(3 Pt 2):R708-15
Exogenously administered
tumor necrosis factor-alpha (TNF-alpha) elicits several symptoms of
generalized infections such
as fever, increased sleep, and anorexia. The aim of the present work was
to localize these effects of TNF-alpha to specific amino acid sequences
of the parent molecule by characterizing the in vivo and in vitro activities
of several synthetic TNF-alpha fragmentsIntracerebroventricular injection
of TNF-alpha elicited dose-dependent fevers and increases in non-rapid-eye-movement
sleep (NREMS) in rabbits. Four fragments also promoted NREMS and five elicited
monophasic fevers. All of the somnogenic fragments share the amino acid
sequence 31-36. In rats, TNF-alpha and one of the fragments [TNF-alpha-(69-100)]
suppressed 12-h food intake. Furthermore, TNF-alpha increased the
expression of the intercellular adhesion molecule-1 and enhanced interferon-gamma-induced
HLA-DR expression in human glioblastoma cell line. In contrast, none of
the fragments possessed these in vitro activities. Our in vivo results
support the concept that there are biologically active regions in
the TNF-alpha molecule. |