SUMMARY IL-1 production (secreted and cell-associated) was measured in monocyte cultures stimulated by a variety of agents in vitro. Monocytes either adherent to conventional plastic culture plates in serumfree conditions, or in suspension in culture medium containing serum were stimulated to produce IL-I during culture. In non-adherent, serum-free conditions, monocytes produced very low or undetectable amounts of IL

SUMMARYThe anti-rheiiraatic gold compounds gold sodium Ihiomalatc (GST) and auranofin (AF) have variable and ofien unpredictable efieets in patients treated forarihriiis As inhibition of intcrleukin-l (IL-1) produclion may be an important effect of these driigs, we investigated their effect on lL-1 production by lipopolysaccharide (LPS) stimulated monocytes In a serum-frcc. non-adhercni culture system. A bi-modal effect was observed: low concentrations (GST 10-^250 ng/ml and AF 1-100 ng/ ml) potentiated IL-I production, and higher concentrations (GST 200-1000 ng/ml and Al-'IO-500 ng/ml) inhibited it This bi-modal effect was observed Tor both secrete-d and cell-associated IL-1 activity with lhe exception that GST failed to inhibit cell-associated IL-I generation. The potentiatmg effect was dependent on the continuous presence of gold for at least the first few hours after LPS stimulation. The inhibitory eiTect of GST was dependent on its presence after LPS stimulaiion while Ihal of AF was evident even ifceUs were prelreaied wilh AF and swashed before exposure to LPS. There was considerable individual variation in IL-1 production in response to LPS as well as in ihe effects of gold on cells from both healthy individuals and patients with arthritis. There was also some overlap in the range of concentrations of gold thai potentiated and inhibited IL-I production, and there was relative insensitivity to the inhibitory effects ofgold in certain individuals. These results may explain some of the variability in the response of patients to chrysotherapy and support further studies to see if these in vitro effcct.s tnight predict clinical response to gold.

Monocyte interleukin-1 (IL-1) production in vitro was studied in 49 patients with rheumatoid arthritis (RA) and 31 controls. Twenty-six of the RA patients were studied prospectively for up to 12 months after beginning chrysotherapy. About half of the patients (group 1) exhibited pretreatment levels of monocyte IL-1 secretion (as measured by bioassay or B-IL-1) significantly higher than that of the controls. Immunoreactive IL-1 (IR-IL-1) levels, however, were similar to controls. Clinical improvement in this group of patients was modest and transient but could be associated with a fall in the level of IL-1 (B-IL-1 and IR-IL-1) secretion. Other RA patients (group 2) appeared to have normal or reduced pretreatment levels of IL-1 secretion. Chrysotherapy resulted in significant clinical improvement within 3 months, and this was associated with an increase in IL-1 (both B-IL-1 and IR-IL-1) secretion by the patients' blood monocytes to normal or supranormal levels. Thus these two groups of RA patients (which differed only in the average duration of disease) had different prognoses in relation to chrysotherapy and the effect of chrysotherapy-induced remission on monocyte IL-1 secretion was opposite. These results suggest that monocyte IL-1 production in vitro reflects changes secondary to the anti-rheumatic effects of chrysotherapy.