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PMID: 9653082 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transforming growth factor beta production is inversely correlated with severity of murine malaria infection.

The Journal of experimental medicine ·Vol. 188 ·No. 1 ·1998-07-06 ·Pages 39-48

Omer FM, Riley EM

Abstract

We have examined the role of the immunomodulatory cytokine transforming growth factor (TGF)-beta in the resolution and pathology of malaria in BALB/c mice. Circulating levels of TGF-beta, and production of bioactive TGF-beta by splenocytes, were found to be low in lethal infections with Plasmodium berghei. In contrast, resolving infections with P. chabaudi chabaudi or P. yoelii were accompanied by significant TGF-beta production. A causal association between the failure to produce TGF-beta and the severity of malaria infection was demonstrated by treatment of infected mice with neutralizing antibody to TGF-beta, which exacerbated the virulence of P. berghei and transformed a resolving P. chabaudi chabaudi infection into a lethal infection, but had little effect on the course of P. yoelii infection. Parasitemia increased more rapidly in anti-TGF-beta-treated mice but this did not seem to be the explanation for the increased pathology of infection as peak parasitemias were unchanged. Treatment of P. berghei-infected mice with recombinant TGF-beta (rTGF-beta) slowed the rate of parasite proliferation and prolonged their survival from 15 to up to 35 d. rTGF-beta treatment was accompanied by a significant decrease in serum tumor necrosis factor alpha and an increase in interleukin 10. Finally, we present evidence that differences in TGF-beta responses in different malaria infections are due to intrinsic differences between species of malaria parasites in their ability to induce production of TGF-beta. Thus, TGF-beta seems to induce protective immune responses, leading to slower parasite growth, early in infection, and, subsequently, appears to downregulate pathogenic responses late in infection. This duality of effect makes TGF-beta a prime candidate for a major immunomodulatory cytokine associated with successful control of malaria infection.

MeSH Terms
Animals Antibodies, Monoclonal/immunology,pharmacology Cytokines/blood Disease Models, Animal Interleukin-10/blood Malaria/physiopathology,therapy Male Mice Mice, Inbred BALB C Monocytes/metabolism Plasmodium/parasitology Recombinant Proteins/metabolism Spleen/metabolism Transforming Growth Factor beta/blood,immunology Tumor Necrosis Factor-alpha/metabolism
Chemicals
Antibodies, Monoclonal Cytokines Recombinant Proteins Transforming Growth Factor beta Tumor Necrosis Factor-alpha Interleukin-10
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Omer F M
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, EH9 3JT United Kingdom.
Riley E M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.188.1.39
Published
1998-07-06
Pages
39-48
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2525539
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.188.1.39 PMC Full Text View journal details
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