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Summary: Background: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal gammopathy, which manifest mostly in the second half of life. It involves overactivation of the interleukin (IL)‐1 system, but the exact pathophysiological pathways remain largely unknown. Objectives: To identify and characterize the pathogenetic players in SchS. Methods: Blood parameters were quantified in patients with SchS compared with healthy controls and patients with psoriasis and hidradenitis suppurativa using enzyme‐linked immunosorbent assay (ELISA). CCL2 expression in cultured primary cells was analysed by quantitative reverse‐transcriptase polymerase chain reaction and ELISA. Results: CCL2, a chemoattractant for monocytic and further mononuclear immune cells, was found to be significantly elevated in patients with SchS. CCL2 levels showed a positive association with global disease activity, especially with bone pain, but not disease duration, gammopathy, neutrophilia or skin disease. In vitro stimulation assays demonstrated a strong CCL2 production capacity of mononuclear immune cells and fibroblasts, but not epithelial or endothelial cells. Among a range of inflammatory mediators, only IL‐1β (immune cells, fibroblasts) and tumour necrosis factor (TNF)‐α (fibroblasts) were important CCL2 inducers. TNF‐α, but not IL‐17, strengthened the CCL2‐inducing effect of IL‐1β in fibroblasts. Accordingly, CCL2 levels positively correlated with both TNF‐α and IL‐1β serum levels in patients with SchS. Therapeutic IL‐1β blockade decreased CCL2 blood levels in these patients as early as 1 week after the initiation of treatment. Conclusions: CCL2 may be an important component of the pathogenetic cascade leading to bone alterations, and a suitable marker of disease activity in patients with SchS. What's already known about this topic?Schnitzler syndrome (SchS) is a very rare acquired autoinflammatory disease, clinically characterized by urticarial exanthema, arthralgia and osteosclerosis, and episodes of fever.The pathogenesis involves overactivation of the interleukin‐1 system.The exact pathogenetic pathways are mostly unknown, and biomarkers are not available to assess the inflammatory activity in SchS. What does this study add? The chemokine CCL2 is a marker of SchS; its blood levels are significantly upregulated and linked to global disease activity and early therapy response in patients with SchS.While no clear relationship with patients' urticarial exanthema was detected, CCL2 may be involved in bone alterations in these patients.The cellular sources of CCL2 include mononuclear immune cells and fibroblasts.Interleukin‐1β and tumour necrosis factor‐α, blood levels of which correlate with CCL2 levels in patients with SchS, are important CCL2 inducers. What is the translational message? Quantifying CCL2 blood levels may allow the objective estimation of inflammatory disease activity and may help with the therapy decision in patients with SchS.CCL2 may be a key element of the pathogenetic cascades in SchS, especially those important for osteosclerosis. Linked Comment:Kambe and Nguyen. Br J Dermatol 2019; 180:706–707. Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]

OBJECTIVE: Major surgery, polytrauma, stroke, and pancreatitis frequently lead to a compensatory anti-inflammatory response syndrome that often predisposes patients to lethal infections. This temporary postinflammatory immunodeficiency is characterized by altered function of blood monocytes. These cells show strongly reduced inflammatory and antigen-presentation capacity. Diminished monocyte expression of the major histocompatibility complex class II molecule human leukocyte antigen (HLA)-DR is a well-established diagnostic marker of this immunodeficiency. To further characterize the monocytic cells in this clinical state, we analyzed their expression of CD86, the most important co-stimulatory molecule. DESIGN: Analysis of blood samples that entered the clinical immunologic diagnostics and of cells from an in vitro model of postinflammatory immunodeficiency. SETTING: University laboratory. SUBJECTS: Healthy donors and intensive care unit (ICU) patients at the university hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The expression of HLA-DR on monocytes and of CD86 and CD80 on monocytes and B cells was analyzed by flow cytometry. Messenger RNA expression of CD86 was analyzed in isolated monocytes by real-time polymerase chain reaction on reverse transcribed. The normal range of monocyte CD86 expression in healthy subjects was established to be from 2128 to 5102 surface molecules per cell and was independent of age, gender, and leukocyte and monocyte count. The CD86 expression on monocytes in ICU patients correlated with HLA-DR expression. Approximately 40% of the ICU patients with long-term reduced monocyte HLA-DR expression had a long-term reduction of CD86 expression. Patients in whom the expression of both molecules was diminished had an unfavorable prognosis. The diminished number of CD86 surface molecules on monocytes was associated with reduced CD86 messenger RNA levels in these cells. The expression of CD86 in B cells was not diminished in immunodeficient patients. The expression of CD80 in both monocytes and B-cells was minimal in healthy donors and not clearly changed in patients. CONCLUSIONS: The monocyte CD86 expression may be a helpful diagnostic variable in ICU patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Insulin-like growth factor I (IGF-I) has been implicated in several chronic diseases, including cancer, heart disease, and osteoporosis. OBJECTIVE: Our aim was to assess whether intakes of total energy, alcohol, vitamins, minerals, and foods rich in protein and minerals (including red meat, fish and seafood, poultry, and milk) are associated with serum IGF-I concentrations in middle-aged and elderly men. DESIGN: We measured serum IGF-I concentrations in 226 free-living healthy men aged 42-76 y. The average of fourteen 24-h dietary telephone interviews performed over 1 y was used to estimate long-term dietary intake. RESULTS: We observed statistically significant positive associations between intakes of protein (P for trend = 0.001) and zinc (P for trend = 0.002) and serum IGF-I concentrations after adjusting for age. The difference in mean IGF-I concentrations for the highest compared with the lowest quintile of intake was approximately 17% (162 microg/L compared with 139 microg/L) for protein and approximately 16% (166 microg/L compared with 143 microg/L) for zinc. Consumption of red meat (P for trend = 0.05) and fish and seafood (P for trend = 0.07) was modestly positively associated with IGF-I concentrations. Other dietary factors were not associated with IGF-I concentrations. CONCLUSION: In this population of healthy well-nourished men, greater dietary intakes of protein, zinc, red meat, and fish and seafood were associated with higher IGF-I concentrations. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]