Parasitology

Research Article

Hepatic fibrosis and gene expression changes induced by praziquantel treatment during immune modulation of Schistosoma japonicum infection

T. F. Kresinaa1*, Qing Hea1, S. Degli Espostia2 and M. A. Zerna3

a1 Department of Medicine, Miriam Hospital, Brown University International Health Institute, Providence, RI 02906, USA

a2 Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA

a3 Department of Medicine, VA Medical Center and Roger Williams Medical Center, Providence, RI 02906, USA

Abstract

In the present study fibrogenic gene expression was determined in murine Schistosoma japonicum infection during the progression of immune modulation of infection and following chemotherapy during the course of immune modulation. Histomorphometric analysis of granuloma size and collagen deposition revealed peak granuloma size in acute infection (5 weeks) and peak hepatic collagen content at 16 weeks of infection. Peak Type I collagen gene expression was concomitant with TGF-β1 gene expression at 8–11 weeks. Chemotherapy during either acute (9 weeks) or chronic (24, 28 weeks) infection resulted in increased collagen deposition and increased gene expression of Type I collagen and TGF-β1. However, chemotherapy at 14–16 weeks resulted in decreased levels of TGF-β1 gene expression and essentially minimal change in Type I collagen deposition and gene expression. These data indicate that chemotherapy of schistosomiasis japonica does not reverse hepatic fibrogenesis when administered in acute infection – when granuloma size is maximal – or in chronic infection. However, a beneficial effect on hepatic fibrogenesis is seen when chemotherapy is administered at 14–16 weeks post-infection, a time of decreasing granuloma size and maximal hepatic collagen content. Thus the ability to reverse schistosomal-induced hepatic fibrogenesis by chemotherapy may depend on disease stage.

(Received December 02 1992)

(Revised March 15 1993)

(Accepted March 22 1993)

Footnotes

* Reprint requests to: Dr Thomas F. Kresina, NIDDK, Digestive Diseases and Nutrition Branch, Westwood Building, Room 3A17, NIH, Bethesda, MD 20892, USA.

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