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We have previously shown that co-culture of T cell enriched spleen lymphocytes can reduce collagen synthesis and stimulate proliferative activity by liver fibroblasts from S. mansoni infected mice. The present study examines which subset of T cells is responsible for this modulation. Co-culture of fibroblasts with the total T cell population lead to significant stimulation in fibroblast proliferative activity and a significant decrease in the incorporation of 14C-proline into collagenase-sensitive protein. There was virtually no effect on total incorporation of 14C-proline in non-collagen proteins. An additional significant increase in fibroblast proliferative activity and another significant decrease in collagen synthesis accompanied by a 2-fold increase in non-collagen protein production was noted when fibroblasts were co-cultured with Lyt-1+ cells. Co-culture of fibroblasts with Lyt-2+ cells did not differ significantly from co-culture with total T cells. Mitomycin treatment of the lymphocytes blunted their specific effects, suggesting that proliferation of T cells is required for maximal exertion of their regulatory activity. These results suggest that the T cells which mediate these effects belong to the Lyt-1+ helper class and are distinct from the Lyt-2+ suppressor cells.

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Colchicine, an antimicrotubular agent, was shown to block the transcellular movement of certain structural macromolecules such as collagen. In the present study, the effect of colchicine on collagen synthesis and secretion by monolayer cultures of fibroblasts from livers of mice infected with Schistosoma mansoni was investigated. The effect of colchicine on proliferation of these fibroblasts was studied as well. Collagen and non-collagen protein synthesis was measured by incubating cultures with [14C]proline and measuring the incorporation of radioactivity into these protein fractions in both culture media and cell layers. Proliferation was measured by [3H]thymidine uptake. The isolated fibroblasts actively formed collagen and secreted most of it into the culture medium; 10-20% of the collagenase-sensitive radioactive protein remained in the cell layer. The addition of colchicine to culture medium led to selective inhibition of collagen formation with negligible effects on non-collagen protein synthesis. Fibroblast proliferation was also reduced by colchicine treatment. Both inhibition of collagen synthesis and inhibition of fibroblast proliferation were dose-dependent. Comparison of medium and cell layer collagen radioactivity confirmed inhibition of synthesis rather than only inhibition of secretion. These data suggest that colchicine has a specific effect on synthesis of collagen and proliferative activity by fibroblasts from S. mansoni-infected liver and may, therefore, be useful in modulating schistosomal hepatic fibrosis.

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Primary cell cultures from the livers of mice infected with Schistosoma mansoni were prepared and cells with the appearance of fibroblasts by light microscopy were isolated. Collagen synthesis was estimated by measuring incorporation of 14C-proline into collagenase-sensitive proteins for both culture media and cell layers. Coculture of splenic T cells from infected mice with these hepatic fibroblasts caused greater selective and specific reduction in collagen production than did coculture using spleen cells from normal mice. There was a parallel inhibition in collagen within the cell layer which indicates that the marked decrease in collagen production was due to inhibition of synthesis and not related to changes in solubility or secretion. Primary culture of mouse skin fibroblasts showed similar responses to coculture but an established fibroblast line, 3T3, was unresponsive. Inflammatory cells appear to influence hepatic fibroblasts isolated under our experimental condition in several ways, such as opposite effects on collagen synthesis and cell proliferation.

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The effect of active schistosomiasis on the activity of some serum enzymes of hepatic origin has been studied in 46 male Egyptian patients with S. mansoni infections. These enzymes included total lactic dehydrogenase and its isoenzymes, 5'nucleotidase, B-glucuronidase, ornithine carbamyl transferase and sorbitol dehydrogenase. Samples were collected on admission, a week after the end of treatment and one month later. B-glucuronidase showed no change whereas ornithine carbamyl transferase, sorbitol dehydrogenase and 5'-nucleotidase showed elevated levels throughout the study. Total LDH was not significantly different on admission but increased significantly after treatment and returned to normal at follow up. Of the five LDH isoenzymes only LDH4 showed elevated levels. The significance of these findings in relation to conventional liver function tests is discussed.

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