leukotriene-b4 and Hidradenitis-Suppurativa

Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent and debilitating skin disease of the hair follicle unit that typically develops after puberty. The disorder is characterized by comedones, painful inflammatory nodules, abscesses, dermal tunnels and scarring, with a predilection for intertriginous areas of the body (axillae, inguinal and anogenital regions). Recruitment of neutrophils to HS lesion sites may play an essential role in the development of the painful inflammatory nodules and abscesses that characterize the disease. This is a review of the major mediators involved in the recruitment of neutrophils to sites of active inflammation, including bacterial components (endotoxins, exotoxins, capsule fragments, etc.), the complement pathway anaphylatoxins C3a and C5a, tumour necrosis factor-alpha, interleukin (IL)-17, IL-8 (CXCL8), IL-36, IL-1, lipocalin-2, leukotriene B4, platelet-activating factor, kallikreins, matrix metalloproteinases, and myeloperoxidase inhibitors. Pharmacological manipulation of the various pathways involved in the process of neutrophil recruitment and activation could allow for successful control and stabilization of HS lesions and the remission of active, severe flares.

Topics: Axilla; Hidradenitis Suppurativa; Humans; Leukotriene B4; Neutrophils; Peroxidase

Hidradenitis suppurativa (HS) is a chronic, recurring inflammatory dermatosis characterized by abscesses, deep-seated nodules, sinus tracts, and fibrosis in skin lesions around hair follicles of the axillary, inguinal, and anogenital regions. Whereas the exact pathogenesis remains poorly defined, clear evidence suggests that HS is a multifactorial inflammatory disease characterized by innate and adaptive immune components. Bioactive lipids are important regulators of cutaneous homeostasis, inflammation, and resolution of inflammation. Alterations in the lipid mediator profile can lead to malfunction and cutaneous inflammation. We used targeted lipidomics to analyze selected omega-3 and omega-6 polyunsaturated fatty acids in skin of patients with HS and of healthy volunteers. Lesional HS skin displayed enrichment of 5-lipoxygenase (LO)‒derived metabolites, especially leukotriene B4. In addition, 15-LO‒derived metabolites were underrepresented in HS lesions. Changes in the lipid mediator profile were accompanied by transcriptomic dysregulation of the 5-LO and 15-LO pathways. Hyperactivation of the 5-LO pathway in lesional macrophages identified these cells as potential sources of leukotriene B4, which may cause neutrophil influx and activation. Furthermore, leukotriene B4-induced mediators and pathways were elevated in HS lesions, suggesting a contribution of this proinflammatory lipid meditator to the pathophysiology of HS.

Topics: Adult; Aged; Arachidonate 15-Lipoxygenase; Arachidonate 5-Lipoxygenase; Biopsy; Cells, Cultured; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Gene Expression Profiling; Hidradenitis Suppurativa; Humans; Inflammation; Leukotriene B4; Lipid Metabolism; Lipidomics; Male; Middle Aged; Primary Cell Culture; Signal Transduction; Skin; Up-Regulation; Young Adult