Inhibition of human lung fibroblast growth by mononuclear cells

We examined in vitro the effect of supernatants from unstimulated, mitogen-stimulated and antigen-stimulated blood mononuclear cells on the growth of fibroblasts from normal adult lungs. Supernatants prepared from mononuclear cells in the absence of mitogen or antigen had no consistent effect on fibroblast growth. Supernatants from mononuclear cells incubated with antigens to which the donor was not sensitive (stimulation index, less than 5) also had no effect on fibroblast proliferation. In contrast, mitogen-stimulated (phytohemagglutinin, concanavalin A, pokeweed mitogen) and antigen-stimulated (purified protein derivative, beryllium sulfate) mononuclear cells (stimulation index greater than 5) inhibited log phase fibroblast growth. The inhibition was mediated by a soluble factor (or factors) that was elaborated within 24 h of initiation of mononuclear cell cultures. The factor was nondialyzable, partially heat labile, and its effect on fibroblast growth may be mediated in part by fibroblast prostaglandin production. The results suggest that inhibition of fibroblast growth by stimulated mononuclear cells may be an important mechanism regulating fibrosis in the lung.