Leukocyte sensitivity to native human interstitial collagen in chronic liver disease

Peripheral blood mononuclear cells and lymphocyte subsets separated from 28 patients with chronic liver diseases, and 11 age and sex matched normal controls were examined for cellular sensitivity to native human interstitial collagens and phytohemagglutinin, non-specific mitogen, by an in vitro leukocyte migration inhibitory test. The leukocyte sensitivity of peripheral blood mononuclear cells to type I, III, and V collagens was significantly higher in patients with chronic liver disease (26 +/- 10%, 25 +/- 11%, and 24 +/- 10%, respectively) than in controls (9 +/- 4%, 10 +/- 6%, and 9 +/- 3%, respectively, p < 0.001). Although the leukocyte sensitivity to phytohemagglutinin was significantly lower in patients with chronic liver disease than in controls (52 +/- 7% vs. 62 +/- 7%, p < 0.01). The leukocyte sensitivity to interstitial collagen in chronic liver disease was neither type specific nor disease specific, but it was correlated with the degree of hepatic fibrosis, or serum concentrations of procollagen type III peptide and 7S domain of type IV collagen. On the other hand, among subsets, the leukocyte sensitivity of T cells was significantly higher than that of B cells (p < 0.01), although there was no difference in leukocyte sensitivity between CD4 and CD8 T cells. These findings demonstrate that cellular immunity to interstitial collagen increases in chronic liver disease, reflecting the increased metabolism of hepatic collagen, in contrast to the pattern of decreased immunity to the non-specific mitogen.