Compartmentalized Cytokine Responses in Hidradenitis Suppurativa

• Published in: PloS one 2015-06, Vol.10 (6), p.e0130522-e0130522
• Main Authors: Kanni, Theodora, Tzanetakou, Vassiliki, Savva, Athina, Kersten, Brigit, Pistiki, Aikaterini, van de Veerdonk, Frank L, Netea, Mihai G, van der Meer, Jos W, Giamarellos-Bourboulis, Evangelos J
• Format: Article
• Language: English
• Subjects: Adult; Blood; Case-Control Studies; Comparative analysis; Cytokines; Cytokines - metabolism; Cytometry; Disease; Epidemiology; Etanercept; Etanercept - therapeutic use; Fc receptors; Female; Flow cytometry; Follow-Up Studies; Gangrene; Hidradenitis Suppurativa - drug therapy; Hidradenitis Suppurativa - metabolism; Hidradenitis Suppurativa - pathology; Humans; Immunosuppressive Agents - therapeutic use; Infections; Inflammation; Interleukin 17; Interleukin-17 - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Internal medicine; Leukocytes (mononuclear); Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Lipopolysaccharide Receptors - metabolism; Male; Medical schools; Medicine; Middle Aged; Monoclonal antibodies; Monocytes; Monocytes - cytology; Monocytes - metabolism; Patients; Post-translation; Receptors, IgG - metabolism; Severity of Illness Index; Tumor necrosis factor; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0130522

Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS). Blood monocytes of 120 patients and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs) were stimulated for cytokine production; this was repeated in 13 severe patients during treatment with etanercept. Cytokines in pus were measured. CD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in Hurley III patients. Cytokine production 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. Findings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF.