Background Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS). by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ indicating post-translational inhibition. The low production of IL-17 was restored when cells were incubated with adalimumab. In pus high concentrations of pro-inflammatory cytokines were detected. Based on the patterns six different cytokine profiles were discerned which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of IL-1β and IL-17 by PBMCs at week 8. Conclusions Findings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF. Introduction Hidradenitis suppurativa (HS) is a chronic devastating skin disorder affecting areas rich in apocrine glands. Nodules appear in the affected areas; they progressively become swollen and rupture with the release of pus. This process occurs repeatedly ending to sinus tract formation and scars [1]. HS seems to indiscriminately affect the global population. Although the exact epidemiology is unknown a recent large epidemiological survey in France reports 0.97% disease prevalence [2]. HS has considerable impact on the quality of life of patients often leading to loss of many working hours per month. The Dermatology Quality Life Index (DQLI) for HS is 8.9 being thus Elacridar higher than any other skin disorder [3]. We have previously demonstrated defective lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokines Elacridar TNFα and IL-6 by blood monocytes of patients with HS [4]. This finding is a paradox since HS skin lesions are heavily inflamed and often they respond to anti-cytokine treatment either with agents blocking TNFα [5] or with agents blocking IL-1β and IL-1α [6]. Puzzled by this paradox the current study was undertaken to better understand the role and the regulation of the various pro-inflammatory cytokines in HS. We wanted to know which monocyte populations and subpopulations (i.e. inflammatory monocytes and patrolling monocytes) are involved. Also we wanted to understand whether peripheral cytokine production is inhibited at the transcriptional or post-transcriptional level and whether this phenomenon of down-regulation is modulated by anti-TNF treatment. Finally we aimed to find out the cytokine profile at the level of the inflammatory lesions by measuring cytokines is pus. Methods Study population Rabbit Polyclonal to OPN4. The study was conducted during the period September 2009 to January 2012 in patients under follow-up in the Outpatient Department of Immunology and Infectious Diseases of the ATTIKON University Hospital (approval 103/24.03.2009). The study was approved by Elacridar the Ethics Committee of the hospital. Written informed consent was provided by all patients and controls. Diagnosis of HS was based on the following criteria: a) onset early after puberty; b) presence of subcutaneous nodules in areas of skin rich in apocrine glands; and c) a compatible history of recurrent drainage of pus from the affected areas [3 7 Clinical characteristics of patients were recorded comprising demographics age since disease onset involved areas and Hurley stage of severity. Lesions were graded according to the clinical system of Hurley [3 7 The severity of the disease was assessed during follow up of these patients according to the scoring system proposed by Sartorius et al [8]. Whole blood was collected from patients after venipuncture of one forearm vein under Elacridar aseptic conditions. Blood sampling was repeated for some patients under treatment with anti-TNF agents. Blood sampling was also performed from 24 healthy volunteers. When available pus was collected from the HS lesions as indicated below. Flow cytometry In Elacridar order to study the monocyte subsets four ml of whole blood were collected into ethylenediamine tetraacetic acid (EDTA)-coated tubes. Whole blood was incubated for 15 minutes in the dark with the flurochrome-conjugated monoclonal antibodies anti-CD14 (FITC emission 525 nm Immunotech Marseille France); anti-CD16 (PE emission 525 nm.