       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).

