UNSTIMULATED PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM PATIENTS WITH THE HYPER-IGD SYNDROME PRODUCE CYTOKINES CAPABLE OF POTENT INDUCTION OF C-REACTIVE PROTEIN AND SERUM AMYLOID A IN HEP3B CELLS

The hyper-IgD and periodic fever syndrome (HIDS) and familial Mediterr anean fever (FMF) are both characterized by attacks of periodic fever accompanied by acute phase responses that are substantially higher in HIDS than in FMF. To determine whether this difference could be due to differences in production of acute phase protein-inducing mediators, we studied PBMC from HIDS and FMF patients in the inactive phase of di sease. Unstimulated PBMC from patients with inactive HIDS released sig nificantly more IL-1 beta, IL-6, and TNF-alpha than did PBMC from pati ents with FMF, but unstimulated PBMC from the latter group released si gnificantly more IL-1 beta and IL-6 compared with controls. Conditione d medium (CM) derived from PBMC of patients with inactive HIDS induced significantly greater CRP production and significantly higher mRNAs f or CRP and SAA in Hep3B cells than did CM derived from the PBMC of pat ients with inactive FMF. Stimulation of PBMC with LPS led to further i ncreases in cytokine production and in acute phase protein-inducing ab ility in both patient groups and in controls. These findings suggest t hat the greater acute phase response seen in HIDS compared with FMF re flects greater production of acute phase protein-inducing cytokines in the former patients and indicates that PBMC from inactive HIDS patien ts are already activated in vivo. Finally, the finding of both quantit ative and qualitative differences in cytokine production by unstimulat ed PBMC from HIDS and FMF patients supports the likelihood of differen t pathogeneses of these diseases.