The effect of bacterial products on synovial fibroblast function: hypermetabolic changes induced by endotoxin

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Abstract
The effects of bacterial products on selected synovial fibroblast functions were studied. Extracts of commonly encountered microorganisms were prepared by sonic or mechanical disruption. "Purified" endotoxins were prepared from selected organisms, and in some cases were purchased commercially. Normal fibroblasts were derived from synovial connective tissue obtained from amputations or arthrotomy. The cells were grown as a monolayer on glass and were nourished by a semisynthetic nutrient medium. Extracts of Gram-negative bacteria, applied to fibroblast cultures, markedly increased hyaluronic acid production, glucose utilization, and lactate output. Treatment of the extracts with heat at 100 degrees C for (1/2) hr decreased their effectiveness by approximately 40%. Purified Gram-negative bacterial endotoxin stimulated synovial fibroblasts to an extent comparable to that caused by heat-treated whole extracts. The lipid moiety of the endotoxin molecule appeared to account for much of the stimulatory activity of the endotoxin. Extracts of commonly encountered Gram-positive cocci, yeast, and Mycoplasma had no stimulating capabilities. Corynebacterial extracts, however, had definite stimulating potential. Endotoxin-synovial cell interaction experiments demonstrated that endotoxin was bound to fibroblasts. Reassay of the endotoxin after extraction from the cells showed that it retained its stimulatory potential. The metabolic phenomena stimulated by bacterial products duplicate the major known actions of connective tissue-activating peptide (CTAP). The observations made in this study suggest that bacterial products may participate in a fundamental way in the activation process, and indicate a possible role for bacterial products in synovial inflammation in humans.