Figure 3
From: An autoinflammatory neurological disease due to interleukin 6 hypersecretion
In vitro IL-1β secretion, serum and cerebrospinal fluid (CSF) IL-6 in the patient, and in vitro IL-6 secretion. (A) IL-1β secretion from monocytes of the proband (II-4), his family members (I-1, I-2, II-1 and II-2) and five unrelated healthy controls (HC1-5) after 3 hours of LPS incubation, or 15 minutes of ATP exposure following LPS stimulation, was quantified by ELISA. Results are expressed as pg/ml per 106 cells. For the proband the values are the mean of three experiments. Unlike monocytes from patients bearing a pathogenic NLRP3 mutation [8], monocytes from the proband and his family members, harboring the p.I288M NLRP3 (I-2 and II-1), p.R761H MEFV (I-1), or both (II-2 and II-4) mutations, displayed a pattern of IL-1β secretion similar to healthy controls, and characterized by further IL-1β secretion following ATP induction. (B) Serum and CSF IL-6 in our patient before and under tocilizumab (TCZ). Before tocilizumab, IL-6 concentration was evaluated in patient’s serum samples (n=7) and CSF samples (n=5), each obtained ≥4 weeks apart. IL-6 was raised in serum (37.20±18.17, normal value (nv) ≤10 pg/ml) and CSF (5432±2742, nv ≤10) despite a high dose of prednisone. CSF IL-6 concentration was very high, and the mean ratio of CSF IL-6/serum IL-6 was about 146, suggesting that IL-6 is produced in central nervous system (CNS). Under tocilizumab (and prednisone reduction ), serum IL-6 concentration significantly increased (178.8±84.14 (n=23) versus 37.20±18.17 (n=7), P= 0.0003; Mann–Whitney test); the slight increase of CSF IL-6 concentration was not significant (7221±2212 (n=4) versus 5432±2742 (n=5), P= 0.2857; Mann–Whitney test). (C) In vitro IL-6 secretion. IL-6 amounts from monocytes of our patient (Pt) and 13 healthy controls (HCs) are similar under resting conditions (RCs; 8.043±3.343 pg/ml (n=7) versus 12.36±8.3) and after LPS stimulation (LPS; 1209±956.6 pg/ml (n=7) versus 772.7±663.2), further suggesting that the deregulation of IL-6 production occurs primarily in CNS. See Additional file 2 for IL-6 mRNA level analysis.