Poly I :C ( polyinosinic-polycytidylic acid) stimulated hyaluronic acid production by rheumatoid and nonrheumatoid human synovial fibroblasts. Stimulation was dose dependent and was inhibited by acetylsalicylic acid and indomethacin. Poly 1 and Poly C, when separately added, had no stimulatory effect on hyaluronic acid production, and Poly A:U had only a slight effect on this parameter. Cells grown with Poly I:C were virus resistant and interferon was detected in their medium. Human interferon had also a dose-dependent stimulatroy effect on hyaluronic acid production by synovial cells. A possible interferon-mediated relationship between virus infection and pathologic accumulation of joint fluid is suggested. Previous studies have shown that addition of leukocytes to human synovial cell cultures caused overproduction of hyaluronic acid by the fibroblasts (l,2), Overproduction of hyaluronic acid could be inhibited by antiinflammatory drugs (3). Castor has described and defined a connective tissue activating peptide (CTAP) that is capable of stimulating hyaluronic acid production by cultured fibroblasts, and he postulated a regulatory role for this peptide in the inflammatory process (4). Hyaluronic acid production by synovial cells in culture may therefore serve as a sensitive parameter for the study of the inflammatory process.A relationship between viral infection and arthritis has been repeatedly mentioned in the literature (5-7). Thus the present authors were prompted to evaluate the effect of Poly 1:C and interferon on hyaluronic acid production by synovial cells in culture. Poly I:C is a high molecular weight double-stranded neucleotide capable of inducing interferon production by various cells (8). MATERIALS AND METHODSFibroblasts derived from synovial membranes of patients with rheumatoid arthritis (rheumatoid cells) or from synovial membrane obtained during meniscus tear operations of otherwise healthy persons (nonrheumatoid cells) were grown in culture by methods previously reported by Castor et a1 (9). T-30 tissue culture flasks (5 ml of medium per flask) with siliconized rubber stoppers were inoculated with 0.5 X 108 fibroblasts and incubated at 37°C. The medium, which was changed once in 2 days, was Parker medium 1066 (80%), heatinactivated human serum (lo%), and fetal calf serum (10%)

Viral peritonitis is an exceptionally rare occurrence in peritoneal dialysis. In fact, up to now, only one case report has been documented in the literature. In a prospective study, peritoneal dialysis effluent (PDE) was specifically cultured for the following viruses: the herpes group of viruses, including herpes simplex types I (HSV) and II, cytomegalovirus (CMV) and varicella-zoster (V-Z), and the enteroviruses group including coxsackie B-5 (Cox B), echo, enterovirus and polio. Cultures were performed under both basal conditions and in the presence of peritonitis. No viral growth was demonstrated. The possible existence of an anti-viral factor in the PDE was therefore raised. In order to investigate this hypothesis, the PDE of 16 patients undergoing intermittent peritoneal dialysis and of 24 patients on continuous ambulatory peritoneal dialysis were examined for anti-viral activity. The method used was analogous to that employed for testing the anti-viral effect of interferon (IFN). The inhibition of the cytopathic effect (CPE) of various viruses was examined in the following tissue cultures: Vero cells (a line of monkey kidney cells) incubated with HSV, vesicular stomatitis virus (VSV) and Cox B; human kidney cells incubated with parainfluenza 3 (Para-3); human foreskin fibroblasts incubated with CMV, HSV and VSV and L-929 (a line of mouse cells) incubated with VSV. As control, unused Dianeal (Travenol, Ashdod, Israel) 1.5 and 4.25 g/dl, normal saline and 5 g/dl dextrose solutions were tested under the same conditions using VSV on Vero. The PDE was also examined for the presence of specific anti-viral antibodies by microneutralization and ELISA tests.(ABSTRACT TRUNCATED AT 250 WORDS)

E coli, shigella, salmonella, and cholera endotoxins stimulated prostaglandin E (PGE) production by cultured human synovial and foreskin fibroblasts. The minimal effective dose of Shigella endotoxin was 2 pg/ ml and a maximal response was observed at 10 pg/ml. PGE stimulation was first detected 7 hours after addition of cholera endotoxin. Stimulation by shigella endotoxin of both PGE and hyaluronic acid production was inhibited by indomethacin and aspirin. The present results suggest that PGE is a mediator of joint inflammation induced by endotoxins.A possible relationship between an infectious agent and joint inflammation has been repeatedly reported (1,2). It is possible that such an agent triggers an inflammatory process which in some cases is subsequently perpetuated by other factors (3). An intriguing observation, which has received no clear explanation, is the relationship between acute and chronic bowel diseases and arthritis (4). It is possible that endotoxins liberated from Gram negative bacteria in the bowel trigger an inflammatory reaction in the synovial membrane.There is ample evidence to suggest that prostaglandins are mediators of the inflammatory process (5,6). Others have reported stimulation of hyaluronic acid induced by bacterial endotoxins in human synovial fibroblast cultures (7). We have recently reported an interrelationship between stimulation of hyaluronic acid (HA) and that of prostaglandin E (PGE) in human cultured synovial fibroblasts (8). A preliminary study showed stimulation of both PGE and hyaluronic acid in human synovial fibroblast cultures by shigella endoThe present study reports the stimulation of prostaglandin E induced by different bacterial endotoxins in synovial and foreskin fibroblast cultures. MATERIALS AND METHODS toxin (9).Fibroblasts derived from synovial membranes obtained during meniscus tear operations of otherwise healthy persons were grown in monolayer cultures by methods previously reported by Castor et a1 (10). Human foreskin fibroblasts were obtained from Dr. Dalia Gurari-Rotman and Professor Michel Revel at the Weizmann Institute of Science, Israel. T-30 tissue culture flasks (5 ml of medium per flask) with siliconized rubber stoppers were inoculated with 0.5 X lo6 fibroblasts and incubated at 37OC. Synovial fibroblasts and HeLa cells were grown in medium CMRL 1066 (Gibco) (~W O ) , heat inactivated human serum (lo%), and fetal calf serum (lo%), supplemented with L-glutamine, penicillin, and streptomycin. Eagle's MEM (90%) with fetal calf serum (10%) was used for the foreskin monolayer cultures. "Purified" endotoxins (lipopolysaccharides) were purchased from Sigma

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