PMID- 10491413
OWN - NLM
STAT- MEDLINE
DCOM- 19991013
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 6
DP  - 1999 Sep
TI  - An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper
      type 2-dominated inflammatory response.
PG  - 777-85
AB  - In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to 
      tissue destruction and fibrosis, which causes much of the morbidity and mortality
      associated with this disease. Here we show the importance of IL-13 in the
      pathogenesis of schistosomiasis, and demonstrate, perhaps for the first time, the
      therapeutic efficacy of an IL-13 inhibitor, sIL-13Ralpha2-Fc, in the control of
      hepatic fibrosis. T-helper type 2 (Th2) cytokines dominate the immune response in
      mice infected with Schistosoma mansoni, yet the specific contributions of IL-13
      and IL-4 to the development of fibrosis were not previously investigated. Our
      studies demonstrate that both cytokines play redundant roles in granuloma
      formation, which explains the ability of IL-4-deficient mice to form granulomas
      around eggs. More importantly, however, these studies demonstrate that IL-13 is
      the dominant Th2-type cytokine regulating fibrosis. IL-13 stimulated collagen
      production in fibroblasts, and procollagen I and procollagen III mRNA expression 
      was decreased in sIL-13Ralpha2-Fc-treated mice. Moreover, the reduction in
      fibrosis observed in IL-4-deficient mice was much less pronounced than that in
      sIL-13Ralpha2-Fc-treated animals. Fibrosis is a major pathological manifestation 
      of a number of allergic, autoimmune, and infectious diseases. Thus, our findings 
      provide evidence that IL-13 inhibitors may be of general therapeutic benefit in
      preventing damaging tissue fibrosis resulting from Th2-dominated inflammatory
      responses.
FAU - Chiaramonte, M G
AU  - Chiaramonte MG
AD  - Schistosomiasis Immunology and Pathology Unit, Laboratory of Parasitic Diseases, 
      National Institute of Allergy and Infectious Diseases, National Institutes of
      Health, Bethesda, Maryland 20892, USA.
FAU - Donaldson, D D
AU  - Donaldson DD
FAU - Cheever, A W
AU  - Cheever AW
FAU - Wynn, T A
AU  - Wynn TA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-13)
RN  - 0 (Procollagen)
RN  - 0 (RNA, Messenger)
RN  - 207137-56-2 (Interleukin-4)
SB  - AIM
SB  - IM
SB  - X
MH  - 3T3 Cells
MH  - Animals
MH  - Cytokines/biosynthesis/genetics
MH  - Female
MH  - Interleukin-13/*antagonists & inhibitors
MH  - Interleukin-4/deficiency
MH  - Liver/metabolism
MH  - Liver Cirrhosis, Experimental/*prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Procollagen/genetics
MH  - RNA, Messenger/analysis
MH  - Schistosomiasis mansoni/complications/immunology/*therapy
MH  - Th1 Cells/immunology
MH  - Th2 Cells/*immunology
PMC - PMC408441
EDAT- 1999/09/24 00:00
MHDA- 1999/09/24 00:01
CRDT- 1999/09/24 00:00
PHST- 1999/09/24 00:00 [pubmed]
PHST- 1999/09/24 00:01 [medline]
PHST- 1999/09/24 00:00 [entrez]
AID - 10.1172/JCI7325 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Sep;104(6):777-85. doi: 10.1172/JCI7325.