IL-11 Induces Th17 Cell Responses in Patients with Early Relapsing-Remitting Multiple Sclerosis.

Clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) is the earliest clinically evident phase of the disease, which may provide valuable insight into the molecular mechanisms of the initiation of the autoimmune response in MS. Our results introduce IL-11 as a new cytokine that plays a role in the autoimmune response in the early phase of the disease. IL-11 is the highest upregulated cytokine in the sera and cerebrospinal fluid from CIS patients, which is also increased in patients with clinically definitive relapsing-remitting MS in comparison with healthy control subjects. Serum IL-11 levels are significantly increased during clinical exacerbations in comparison with remissions in the same patients. CD4(+) cells represent a predominant cell source of IL-11 in the peripheral circulation, and the percentage of IL-11(+)CD4(+) cells is significantly increased in CIS patients in comparison with healthy control subjects. Furthermore, we have identified IL-11 as a new Th17-promoting cytokine, because it induces a differentiation of naive CD4(+) T cells into Th17 cells, as well as expansion of Th17 memory cells. Because the Th17 cytokines IL-17F, IL-21 and TNF-α, and TGF-ß induce differentiation of naive cells in the IL-11-secreting CD4(+) cells, we propose that cross-talk between IL-11(+)CD4(+) and Th17 cells may play a role in the inflammatory response in relapsing-remitting MS.

Intrathecal levels of IL-6, IL-11 and LIF in Alzheimer's disease and frontotemporal lobar degeneration.

Cerebrospinal fluid (CSF) levels of interleukin (IL)-6, IL-11 and leukaemia inhibitory factor (LIF) were evaluated in 43 patients with Alzheimer's disease (AD) and 24 patients with frontotemporal lobar degeneration (FTLD) as compared with 30 agematched controls (CON), and correlated with clinical and demographic data and with CSF biomarkers amyloid beta (A beta)42, total tau and tau phosphorylated at position 181 (P-tau). CSF IL-11 mean levels were significantly increased in AD and FTLD as compared with CON (6.5 +/- 4.6 and 6.6 +/- 5.1 versus 3.1 +/- 3.3 pg/ml, P = 0.009). IL-6 mean levels did not differ between patients and CON (P > 0.05),whereas LIF levels were not detectable in patients or in CON. In AD patients, a significantly positive correlation between MMSE scores and IL-11 CSF concentration was observed (r = 0.344, P = 0.028). No correlations with CSF A beta 42, total tau and P-tau were found. IL-11, but not IL-6 levels are increased in AD and FTLD, and the highest peaks were observed in patients with a less severe degree of cognitive deterioration, therefore suggesting a role of this cytokine in early phases of neurodegeneration.

Plasma interleukin 11 levels correlate with outcome of spontaneous intracerebral hemorrhage.

BACKGROUND: Interleukin (IL) 11 is a multipotential cytokine with anti-inflammatory and fibrogenic properties. It is released into the peripheral blood from damaged brain tissue. The objective of this study was to determine plasma and cerebral spinal fluid (CSF) levels of IL-11 in patients with spontaneous intracerebral hemorrhage (ICH) and to correlate IL-11 with survival, related edema of the brain, volume of hematoma, and hydrocephalus. METHODS: Forty-three patients with spontaneous ICH were included. Twenty-three were male, and 20 were female. The mean age of the patients was 64.3 years. Plasma and CSF samples were collected on the first, second, third, and fourth days after spontaneous ICH onset. RESULTS: The levels of IL-11 in CSF (123.9 +/- 107 pg/mL) were 5 times higher than those in plasma (25.5 +/- 18.0 pg/mL) on the first day (P = .001 by paired t test) in our spontaneous ICH patients, and this significant difference persisted up to the third day of ICH. Plasma IL-11 levels in the nonsurvival group (41.2 +/- 18.9 pg/mL) were significantly higher than those in the survival group (22.2 +/- 15.2 pg/mL) on the second day of ICH onset (P = .024 by Mann-Whitney U test), and the significant difference extended to the fourth day. Plasma IL-11 levels of the hydrocephalus group were higher than those of the nonhydrocephalus group in the first 4 days of ICH, but the difference was not statistically significant. CONCLUSIONS: IL-11 was highly associated with mortality caused by spontaneous ICH and correlated with the hydrocephalus occurring after ICH onset. It is our belief that IL-11 can be a useful clinical marker for spontaneous ICH patients.