FIBROCYTE RESPONSE TO INTERLEUKIN-1 STIMU LATION IN KERATOCONUS

Background The reduced mechanical strength of the tissues around a ker atoconus and the ultrastructural disorganization of its matrix compone nts are caused by proteolytic breakdown and incomplete repair. In most biochemical studies on this subject, reduced collagen content and inc reased collagenase and gelatinase activity have been reported. Methods Since interleukin-1 (IL-1) promotes secretion of prostaglandin E-2 (P G-E2 and collagenase, we were interested in the number of membrane rec eptors for these cytokines on keratoconus fibroblasts and determined t he corresponding dissociation constant (k(D)). We also studied the kin etics of cyclo-oxygenase and the synthesis of PG-E2, IL-1 and collagen . We compared the data with data from normal human corneas. Results 1) There was a significant difference (P < 0.05) between the specific bi nding of [I-125]-IL-1 in keratoconic and normal corneal cells. In kera toconus, the number of receptors was four times higher (7000 +/- 100 b inding sites per cell) than in normal corneas (1540 +/- 100 binding si tes per cell). However, there was little difference between the dissoc iation constants for keratoconic ([6.21 +/- 0.5].10 (-11)) and normal ([6.27 +/- 0.5].10 (-11)) corneal cells. 2) Under the study conditions , interleukin-1 was found neither in normal nor in keratoconic cornea. 3) Synthesis of PG-E2 without stimulation of cells by IL-1, which was observed in 8 corneas with and 8 without keratoconus, showed that ker atoconus cells secrete ten times more PG-E2 than normal corneals cells . If IL-1 is added to the incubation medium, which contains [3H]-label ed arachidonic acid, PG-E2 synthesis increases more than in normal cor neal cells. 4) After adding IL-1, the collagen concentration in kerato conus cells in culture was more pronounced than in normal corneal cell s. Conclusions It is still not known why the anomalies discussed above occur in keratoconus. The increase in IL-1 receptor expression and th e high level of cyclooxygenase activity are very probably due to genet ic causes, because they are observed even after 40 generations of cell cultures.