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1996-03-04
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Document 0705
DOCN M9640705
TI A Th1-associated increase in tumor necrosis factor alpha expression in
the spleen correlates with resistance to blood-stage malaria in mice.
DT 9604
AU Jacobs P; Radzioch D; Stevenson MM; Institute of Parasitology, McGill
University, Ste. Anne de; Bellevue, Montreal, Quebec, Canada.
SO Infect Immun. 1996 Feb;64(2):535-41. Unique Identifier : AIDSLINE
MED/96145076
AB We investigated the kinetics of tissue-specific mRNA expression and
systemic production of tumor necrosis factor alpha (TNF-alpha) and the
kinetics of splenic expression of mRNAs of gamma interferon (INF-gamma)
and interleukin-4 (IL-4), cytokines that may regulate TNF-alpha
production, during the early phase of blood-stage infection with
Plasmodium chabaudi AS. Northern blot analysis revealed that resistant
C57BL/6 mice, which clear the infection by 4 weeks, had higher levels of
TNF-alpha mRNA in the spleen and liver early during infection that did
susceptible A/J mice, which succumb to the disease 10 days after
initiation of infection. Treatment of resistant mice with a polyclonal
anti-TNF-alpha antibody confirmed the protective role of TNF-alpha early
during the course of infection. Furthermore, resistant C57BL/6 mice also
expressed high levels of mRNA of IFN-gamma (a Th1 marker) and low levels
of mRNA of IL-4 (a Th2 marker) in the spleen, whereas susceptible A/J
mice had low levels of IFN-gamma mRNA but high levels of TNF-alpha mRNA
in the liver and had high levels of TNF-alpha protein in serum, as
measured by enzyme-linked immunosorbent assay, later during infection
just before death occurred. These results demonstrate that a
Th1-associated increase in TNF-alpha mRNA expression in the spleen early
during infection correlates with resistance to P. chabaudi AS, whereas
increased TNF-alpha mRNA levels in the liver and excessive levels of the
TNF-alpha protein in serum later during infection correlate with
susceptibility. Thus, the role of the TNF-alpha during malaria appears
to depend on the timing and site of its expression and the presence of
cytokines regulating its production.
DE Animal Female Interferon Type II/GENETICS Interleukin-4/GENETICS
Liver/METABOLISM Malaria/*IMMUNOLOGY Male Mice *Plasmodium chabaudi
RNA, Messenger/ANALYSIS Spleen/*METABOLISM Support, Non-U.S. Gov't
Th1 Cells/*PHYSIOLOGY Tumor Necrosis Factor/*BIOSYNTHESIS/GENETICS
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).