Serum Concentrations Of IL-22 Research Articles

Blockade of IL-22 signaling reverses erythroid dysfunction in stress-induced anemias.

Patients with myelodysplastic syndromes (MDS) display severe anemia but the mechanisms underlying this phenotype are incompletely understood. Right open-reading-frame kinase 2 (RIOK2) encodes a protein kinase located at 5q15, a region frequently lost in MDS del(5q) patients. Here, we show that hematopoietic cell-specific haploinsufficient deletion of Riok2 (Riok2f/+Vav1cre) led to reduced erythroid precursor frequency leading to anemia. Proteomic analysis of Riok2f/+Vav1cre erythroid precursors suggested immune system activation and transcriptomic analysis revealed an increase in p53-dependent interleukin-22 (IL-22) in Riok2f/+Vav1cre CD4+ T cells (TH22). Further, we discovered that the IL-22 receptor, IL-22RA1, was unexpectedly present on erythroid precursors. Blockade of IL-22 signaling alleviated anemia not only in Riok2f/+Vav1cre mice but also in wild-type mice. Serum concentrations of IL-22 were increased in the subset of del(5q) MDS patients as well as patients with anemia secondary to chronic kidney disease (CKD). This work reveals a possible therapeutic opportunity for reversing many stress-induced anemias by targeting IL-22 signaling.

Decreased Serum Level of Interleukin-22 Correlates with Hepcidin in Patients with Hidradenitis Suppurativa.

Current understanding of the underlying pathophysiology of hidradenitis suppurativa (HS) links the disease with proinflammatory activation and autoimmune processes. This study investigated serum levels of interleukin (IL)-22, a cytokine critically involved in epithelial homeostasis, in the context of the broad clinical spectrum of patients with HS. The study also assessed the relationship between serum IL-22 and pro-inflammatory activation (as evidenced by serum level of IL-6) and serum hepcidin (central regulator of systemic iron homeostasis). Serum concentrations of IL-22 were assessed in 74 patients with HS and 15 healthy subjects. Compared with healthy controls, patients with HS demonstrated decreased levels of serum IL-22 (median; interquartile range (IQR): 12.4 pg/ml (9.8; 23.5) vs 34.8 pg/ml (24.8; 39.8), p < 0.001 vs controls). Disease severity (assessed both with Hurley staging and Hidradenitis Suppurativa Severity Index) did not differentiate IL-22 levels (p > 0.1 in both comparisons). Serum levels of IL-22 and IL-6 did not correlate with each other (R=–0.17, p = ns). In a subgroup of 24 patients with HS with pro-inflammatory activation, the mean level of IL-22 was similar to that of the remaining patients (median (IQR): 9.8 pg/ml (8.5; 15.0) vs 12.0 pg/ml (9.4; 16.3), p = ns). Patients with HS demonstrated a decreased level of hepcidin (mean: 31.3 ± 25.9 pg/ml), which correlated with the levels of IL-22 (R=0.36, p < 0.05). Patients with HS demonstrated significantly decreased levels of serum IL-22, which was neither correlated with pro-inflammatory status nor associated with disease severity, but correlated modestly with serum hepcidin.

Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn’s Disease: A Phase 2a Study

MEDI2070 is a human monoclonal antibody that selectively inhibits interleukin 23 (IL23), a cytokine implicated in the pathogenesis of Crohn's disease (CD). We analyzed its safety and efficacy in treatment of CD in a phase 2a study. We conducted a double-blind, placebo-controlled study of 119 adults with moderate to severe CD failed by treatment with tumor necrosis factor antagonists. Patients were randomly assigned (1:1) to groups given MEDI2070 (700 mg) or placebo intravenously at weeks 0 and 4. Patients received open-label MEDI2070 (210 mg) subcutaneously every 4 weeks from weeks 12 to 112. The CD Activity Index was used to measure disease activity. The primary outcome, clinical response (either a 100-point decrease in CD Activity Index score from baseline or clinical remission, defined as CD Activity Index score <150) at week 8 occurred in 49.2% of patients receiving MEDI2070 (n= 59) compared with 26.7% receiving placebo (n= 60; absolute difference, 22.5%; 95% confidence interval, 5.6%-39.5%; P=.010). Clinical response at week 24 occurred in 53.8% of patients who continued to receive open-label MEDI2070 and in 57.7% of patients who had received placebo during the double-blind period and open-label MEDI2070 thereafter. The most common adverse events were headache and nasopharyngitis. Higher baseline serum concentrations of IL22, a cytokine whose expression is induced by IL23, were associated with greater likelihood of response to MEDI2070 compared withplacebo. In a phase 2a trial of patients with moderate to severe Crohn's disease who had failed treatment with tumor necrosis factor antagonists, 8 and 24 weeks of treatment with MEDI2070 were associated with clinical improvement. ClinicalTrials.gov ID: NCT01714726.

Involvement of T Helper 17 Cells in D-Penicillamine–Induced Autoimmune Disease in Brown Norway Rats

Idiosyncratic drug reactions (IDRs) are poorly understood, but their clinical characteristics suggest that they are immune mediated. Penicillamine-induced autoimmunity in Brown Norway rats has been utilized as an animal model for mechanistic studies of one type of IDR because it closely mimics the autoimmune syndromes that it causes in humans. Our previous work suggested that it is T-cell mediated. It has been shown that T helper 17 (Th17) cells play a central role in many types of autoimmune diseases. This study was designed to test whether Th17 cells are involved in the pathogenesis of penicillamine-induced autoimmunity and to establish an overall serum cytokine/chemokine profile for this IDR. In total, 24 serum cytokines/chemokines were determined and revealed a dynamic process. In sick animals, interleukin (IL) 6 and transforming growth factor-β1, known to be driving forces of Th17 differentiation, were consistently increased at both early and late stages of penicillamine treatment; however, no significant changes in these cytokines were observed in animals that did not develop autoimmunity. IL-17, a characteristic cytokine produced by Th17 cells, was increased in sick animals at both the messenger RNA and serum protein level. In addition, serum concentrations of IL-22, another characteristic cytokine produced by Th17 cells, were found to be elevated. Furthermore, the percentage of IL-17-producing CD4 T cells was significantly increased but only in sick animals. These data strongly suggest that Th17 cells are involved in penicillamine-induced autoimmunity. Such data provide important mechanistic clues that may help to predict which drug candidates will cause a relatively high incidence of such autoimmune IDRs.

Is interleukin-22 a possible indicator of chronic heart failure's progression?

Chronic heart failure (CHF) is a complex and heterogeneous clinical syndrome and because of its rising incidence and prevalence, it can be considered a global epidemic. Interleukin (IL)-22 is a pro-inflammatory cytokine, belonging to the IL-10 family. Forty-seven consecutive older patients, hospitalized with an admitting diagnosis of CHF at the Geriatric Medicine Unit (University of Messina, Italy), from 01/01/06 to 30/06/06, were enrolled in the study. Serum concentrations of IL-22 were measured by a quantitative enzyme immunoassay technique. IL-22 levels in all CHF patients were significantly higher than those in controls, in particular, only the II and III NYHA class had IL-22 values significantly higher than the controls, whereas there was no difference between the IL-22 levels of NYHA class IV and the controls. The reason may be the declining immune function in CHF older patients, in fact we can hypothesize that the fall in IL-22 levels, with the progression of NYHA class, is due to the reduced ability in CHF patients to respond to infections, as IL-22 has anti-microbial properties. We detected different outcomes correlated to different IL-22 levels, and the Kaplan–Meier curves suggest a trend.