Cytokine regulation of schistosome-induced granuloma and fibrosis.
Schistosomiasis mansoni, a major cause of hepatic fibrosis in many developing countries, triggers a granulomatous inflammatory reaction in response to its eggs that lodge in the liver. The egg antigens are eliminated slowly, and the persistent granulomatous response leads to prolonged matrix synthesis and hepatic fibrosis. In mice, soluble egg antigens (SEA) induce interleukin 4 synthesis, promoting a dominant T helper type 2 lymphocyte accumulation with the release of additional cytokines (IL-5, IL-10), which not only suppress Th1 lymphocyte subset cytokines, but mediate the characteristic pathophysiology. Manipulation of the cytokine profile with antagonists or exogenous cytokine delivery alters the course of the hepatic inflammation and fibrosis. In the evolution of the granulomatous response to the S. mansoni eggs, transforming growth factor beta (TGF-beta) is also produced that may modulate inflammation and regulate fibrogenesis. In TGF-beta 1-gene targeted mutant mice that over-express TGF-beta 1 (TGF-beta 1 transgenics) or in which TGF-beta 1 has been inactivated (TGF-beta 1-/-; null mutation) or partially inactivated (TGF-beta 1+/-; null mutation heterozygotes), the altered production of TGF-beta 1 impacts on S. mansoni granuloma and hepatic fibrosis. In addition to the Th1/Th2 cytokine balance, modulation of TGF-beta 1 may change the outcome of chronic inflammatory fibrotic disease.
Wahl
S M
SM
Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA. smwahl@yoda.nidr.nih.gov
Frazier-Jessen
M
M
Jin
W W
WW
Kopp
J B
JB
Sher
A
A
Cheever
A W
AW
D000818:Animals; D006099:Granuloma / Q000209:etiology*; D008103:Liver Cirrhosis / Q000209:etiology*; D051379:Mice; D012555:Schistosomiasis mansoni / Q000150:complications*; D013601:T-Lymphocytes / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
D016212:Transforming Growth Factor beta