IL-18 Serum Level in Adult Onset Still’s Disease: A Marker of Disease Activity

Abstract

Introduction. Immunological factors seem to play a pivotal role in Adult Onset Still's Disease (AOSD). Among all, IL-18 cytokine is overexpressed and drives the inflammatory process. Objective. We aimed to investigate the levels of IL-18 in sera of Italian patients with AOSD and to assess its possible role as a marker of disease activity. Methods. IL-18 serum levels were determined by ELISA in 26 Italian patients with AOSD. Disease activity was assessed using Pouchot's criteria. As controls, 21 patients with Rheumatoid Arthritis (RA), 21 patients with Sjogren's Syndrome (SS), 20 patients with Systemic Lupus Erythematosus (SLE), and 21 healthy subjects (normal human sera, NHS) were evaluated. Results. IL-18 serum levels were significantly higher in patients with active AOSD than in non-active (P = 0.001) and control groups (RA P = 0.0070, SS P = 0.0029, SLE P = 0.0032, NHS P = 0.0004). A significant correlation between IL-18 serum levels and disease activity (P < 0.0001), and laboratory parameters as ferritin (P = 0.0127) and C-reactive protein (P = 0.0032) was demonstrated. Conclusions. Higher levels of IL-18 are detected in active AODS patients and correlate with disease activity and inflammatory laboratory features. ROC-AUC analysis of the serum concentration of IL-18 suggests that it can be considered a diagnostic marker of AOSD. This paper supports the targeting of this cytokine as a possible therapeutic option in AOSD.

Chronic Fever with Severe Weakness - A Case Report

“…But his productive cough, oral ulceration, muscle cramp, weight loss (10.15%) indicate inflammatory process continued and release of inflammatory mediators. 10 Of all patients with Still's disease, 100% patient have high intermittent fever, 40-45% have hepatosplenomegaly 5,8,10 , 85% have a marked Leukocytosis, hepatomegaly, progressively rising erythrocytes sedimentation rate and ferritin level appears to correlate well with the activity of illness. 8,10,15 The underlying mechanism of this is probably continuation of inflammatory process.…”

“…10 Of all patients with Still's disease, 100% patient have high intermittent fever, 40-45% have hepatosplenomegaly 5,8,10 , 85% have a marked Leukocytosis, hepatomegaly, progressively rising erythrocytes sedimentation rate and ferritin level appears to correlate well with the activity of illness. 8,10,15 The underlying mechanism of this is probably continuation of inflammatory process. A hallmark of AOSD is neutrophil 10 and macrophage activation 15 possibly under the effects of the proinflammatory interleukin-18 (IL-18) signalling.…”

“…A hallmark of AOSD is neutrophil 10 and macrophage activation 15 possibly under the effects of the proinflammatory interleukin-18 (IL-18) signalling. 9,10,14,15 Patients with AOSD often show hypercomplementaemia, and serum levels of IL-1â, IL-6, IL-18, TNFá, IFN " and macrophage-colony stimulating factor (M-CSF) have been found to be considerably higher 10,13 than compared with controls. 14,15 These cytokines also appear to share a role in increasing the production of ferritin.…”

“…14,15 These cytokines also appear to share a role in increasing the production of ferritin. 10,15 The laboratory investigations can show an increased systemic inflammatory response 12 , such as high white blood cell count (usually 10,000 to 15,000 with more than 80% granulocytes), thrombocytosis, low hemoglobin, ESR and significant increase in serum ferritin level. 2,6,9 ESR level could be >100 mm in some cases.…”

“…6 The serum ferritin level has been suggested as a predictive marker for AOSD as it is invariably elevated and often higher than levels found in other autoimmune or inflammatory diseases, with a five-fold increase in serum ferritin being 41% specific and 80% sensitive as a diagnostic test. 15 The markedly high ferritin level in AOSD has been attributed to hyper-production by the reticuloendothelial system or hepatocyte damage, 6,10,13 and is unrelated to iron metabolism. 18 The patient's blood results illustrated a microcytic anemia, although the iron studies point towards an inflammatory reaction.…”