The Role of Soluble Interleukin (IL)-6 Receptor in Mediating the Effects of IL-6 on Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 Expression by Gingival Fibroblasts

Background: Interleukin-6 (IL-6) is a multifunctional cytokine thought to play a role in the tissue destruction that characterizes periodontal disease. IL-6 exerts its cellular effects through a cell-surface receptor which also exists in a soluble from (sIL-6r). This study investigated the effects of IL-6 on matrix metalloproteinase (MMP)-1 activity in gingival fibroblast cultures, specifically determining the role of the sIL-6r in mediating these actions.

Methods: Fibroblasts were grown to confluence, washed in Hank's balanced saline solution (HBSS), and then cultured for 72 hours in serum-free medium supplemented with 0.2% bovine serum albumin, 1 µg/ml Escherichia coli LPS and containing various combinations of IL-6 and its soluble receptor over the concentration range 0 to 1,000 ng/ml. MMP-1 and tissue inhibitor of MMP (TIMP)-1 protein levels in the conditioned medium were assessed by enzyme-linked immunosorbent assay (ELISA) and collagenolytic activity determined using a 3H-acetylated type 1 collagen degradation assay.

Results: Results indicated that the addition of IL-6 alone to cultures, over the concentration range 0 to 1,000 ng/ml, had no significant effect on MMP-1 protein expression. However, addition of IL-6 in combination with its soluble receptor resulted in a statistically significant, dose-dependent upregulation in MMP-1 expression. The IL-6/slL-6r combination also induced a significant increase in collagenolytic activity in cultures. IL-6 and slL-6r, either alone or in combination, had no marked effect on TlMP expression or cell growth.

Conclusions: These data strongly suggest that future clinical studies investigating the role of IL-6 in periodontal disease must also determine the levels of slL-6r within the periodontal tissues. J Periodontol 2002;73:741-747.