Immunological basis of septal fibrosis of the liver in Capillaria hepatica-infected rats

Abstract

Rats infected with the helminth Capillaria hepatica regularly develop septal fibrosis of the liver similar to that induced by repeated ip injections of pig serum. Fibrosis starts when the focal parasitic lesions begin to show signs of resorption, thus suggesting an immunologically mediated pathogenesis of this fibrosis. To explore this possibility, the development of C. hepatica-related hepatic fibrosis was observed in rats exposed to worm antigens from the first neonatal day onward. Wistar rats (150 g) were either injected ip with an extract of C. hepatica eggs (protein concentration: 1 mg/ml) or received immature eggs by gavage from the first neonatal day until adult life and were then infected with 500 embryonated eggs. Changes were monitored on the basis of serum levels of anti-worm antibodies and hepatic histopathology. Rats submitted to immunological oral tolerance markedly suppressed C. hepatica-related serum antibodies and septal fibrosis of the liver when infected with the helminth later on. Tolerance trials with ip injections of worm antigens gave essentially negative results. The partial suppression of septal fibrosis of the liver after the induction of immunological tolerance to C. hepatica antigens in rats indicates an immunological basis for the fibrosis and emphasizes the importance of immunological factors in the pathogenesis of hepatic fibrosis.

Capillaria hepatica in rats: focal parasitic hepatic lesions and septal fibrosis run independent courses

“…Similar lines of evidences have been produced for the septal fibrosis as- sociated with C. hepatica infection of rats (Lemos et al 2003), but the immunology of C. hepatica infection itself is still poorly understood. Repeated experimental infections have resulted in considerable modifications in the constitution of the focal parasitic lesions, while the dynamics and structure of the septal fibrosis were not much altered (Oliveira et al 2004).…”

Capillaria hepatica-induced hepatic fibrosis in rats: paradoxical effect of repeated infections

“…Apparently humoral factors (serum antibodies against C. hepatica) are not involved, unless they acted in a negative way, since their concentration increased in the serum during re-infections. The morphological findings now observed are strikingly similar to those in rats made tolerant to C. hepatica by neonatal contact with the homologous antigens, as described by Lemos et al 11 . In both cases there occurred interference with worm development and a marked decrease in inflammation and fibrosis.…”

“…Septal fibrosis induced by pig-serum was considered to have an immunological basis, because it did not form in animals rendered tolerant to pig-serum 3 . Similar results were obtained for the C. hepatica-induced septal fibrosis by Lemos et al 11 . However, the mechanisms of fibrosis production, the immunological factors involved, have not yet been determined.…”

Experimental hepatic fibrosis due to Capillaria hepatica infection (differential features presented by rats and mice)

“…Septal fibrosis of the liver in C. hepatica-infected rats, although more marked, has the same distribution, and probably the same pathogenetic connotation (Lemos et al 2003) of that induced in rats by repeated injections of whole pig serum or by its albumin fraction (Ballardini et al 1983, Andrade 1991, Bhunchet et al 1992, Paronetto & Popper 1996. Actually, the C. hepatica and the pig-serum models are the two models of septal fibrosis being used in experimental investigations.…”

“…Besides the focal necro-inflammatory parasitic lesions, caused by groups of worms that usually die and disintegrate within the liver soon after egg lying, there also occurs the development of septal fibrosis throughout the liver, a change that appears in all infected rats (Oliveira & Andrade 2001). The model has permitted studies on pathogenesis (Santos et al 2001, Lemos et al 2003, on response to drugs (Souza et al 2000,2001) and on other aspects (Ferreira & Andrade 1993, Oliveira & Andrade 2001. However, the potential of the model is somewhat limited by the peculiarities connected with the experimental host -the rat -because of the difficulties related to the obtaining of commercial kits to study cytokines, chemokines, receptors, growth factors, cells and extra-cellular tissue markers, and so on.…”