LEVELS OF SYNOVIAL-FLUID INTERLEUKIN-1 RECEPTOR ANTAGONIST IN RHEUMATOID-ARTHRITIS AND OTHER ARTHROPATHIES - POTENTIAL CONTRIBUTION FROM SYNOVIAL-FLUID NEUTROPHILS

Objective. To measure synovial fluid (SF) levels of interleukin-1 rece ptor antagonist (IL-1ra) and to determine the capacity of SF neutrophi ls (PMN) to synthesize and release IL-1ra. Methods. A sensitive and sp ecific enzyme-linked immunosorbent assay was used to measure SF IL-1ra protein concentrations and IL-1ra production by isolated SF PMN. Resu lts. SF IL-Ira levels were elevated in 13 of 16 samples from patients with rheumatoid arthritis (RA) (mean 17.1 ng/ml), in 6 of 18 samples f rom patients with infectious or inflammatory, non-RA arthropathies (me an 10.6 ng/ml), and in none of 11 noninflammatory SF samples. SF IL-1r a levels correlated with SF PMN concentrations (r = 0.680, P < 0.00001 ). Isolated SF PMN contained preexisting IL-1ra protein in the absence of messenger RNA (mRNA). In addition, both lipopolysaccharide and gra nulocyte-macrophage colony-stimulating factor induced modest increases in IL-1ra mRNA by cultured SF PMN. Conclusion. IL-1ra levels are incr eased in >80% of RA SF samples. SF PMN produce IL-1ra, possibly contri buting to the levels of IL-1ra present within the SF.