Polypeptide growth factors augment interleukin 1-induced release of prostaglandin E2 by rheumatoid arthritis synovial cells in vitro.
When stimulated with increasing amounts of interleukin 1 beta (IL 1 beta) rheumatoid arthritis (RA), as compared with osteoarthritis (OA), synovial cells grown in RPMI plus fetal bovine serum (FBS), released significantly more prostaglandin E2 (PGE2) (p less than 0.05; paired t test, two-tailed). PGE2 release by IL 1 beta-stimulated RA synovial cells grown for 14 days in serum-free RPMI was significantly less than that released by the same cells grown in medium plus 10% FBS (p less than 0.03; two-tailed). Since these data suggest that growth factors present in FBS may augment the effects of IL 1 beta, experiments were conducted to study the influence of four polypeptide growth factors--transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), on IL 1 beta-induced release of PGE2 by cultured RA synovial cells. Both EGF and bFGF significantly enhanced IL 1 beta-induced release of PGE2 (p less than 0.05; paired t test, one-tailed), while PDGF was synergistic with IL 1 beta, significantly increasing release of PGE2 by these cultured cells (p less than 0.02; two-tailed). No such effect was seen when TGF-beta was added to the culture medium. Taken together, these data lend support to the concept that within the synovial micro-environment small quantities of individual growth factors may potentiate the effects of IL 1 beta to amplify intra-articular inflammation.
Goddard
D H
DH
Einstein-Moss Arthritis Center, Albert Einstein Medical Center, Philadelphia, PA 19141.
Grossman
S L
SL
Newton
R
R
D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D010003:Osteoarthritis / Q000503:physiopathology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D013583:Synovial Membrane / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D006133:Growth Substances; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D015232:Dinoprostone