A case for IL-6, IL-17A, and nitric oxide in the pathophysiology of Sjögren’s syndrome

Abstract

Sjögren's syndrome (SS) is an autoimmune epithelitis characterized by mononuclear cell (MNC) infiltration of the lacrimal and salivary glands (SG), as well as the presence of serum autoantibodies. This condition is a growing public health concern in Algeria. Herein, we sought to determine if the levels of interleukin (IL)-6, IL-17A, and nitric oxide (NO), were correlated with the extent of MNC infiltration. The expression of inducible NO synthase (NOS2) and CD68 was measured in the SG of all patients, but not in those of the normal controls (NCs). We included 44 primary Sjögren's syndrome (pSS) patients and 15 NCs in this study; we found that the expression of NOS2 and CD68 was elevated in all of the SG of SS patients. Additionally, the serum and saliva levels of IL-6, IL-17A, and NO were higher in the pSS patients, compared with the NCs. Furthermore, the NOS2-induced excess NO was associated with the extent of the MNC infiltration, and thereby with tissue injury. It is also important to note that there were correlations between the levels of IL-6, IL-17A, and NO. Such findings indicate that through the effects of NO, IL-17A participates in the pathophysiology of the disease. With the purpose of improving both the diagnosis and prognosis, IL-6, IL-17A, and NO should be assayed in the serum and saliva of patients suspected of SS.

Increased B-cell activating factor, interleukin-6, and interleukin-8 in induced sputum from primary Sjögren’s syndrome patients

“…The level of IL-6 in induced sputum supernatant was also increased in pSS patients, in line with its proposed contribution to lymphocytic infiltration in salivary glands in pSS (13,36), as well as germinal centre (GC) formation (13). GC formation in the small airways can, for example, lead to bronchiolitis and bronchial obstruction, as frequently demonstrated in pSS patients (1,3,4,6).…”

Expression of interleukin‐17 in primary Sjögren's syndrome and the correlation with disease severity: A systematic review and meta‐analysis

“…In addition, we record all reasons for study exclusion, disagreements between the 2 reviewers and third reviewer comments. Finally, 45 articles covering 65 studies are included in the meta‐analysis, with 31 articles including non‐sicca controls, 4 including non‐SS controls and 9 including both types of controls. The other included study compares IL‐17 expression between patients with pSS with weak or strong lymphocytic infiltration, although no control is involved.…”

Upregulation of IL‐6 expression in human salivary gland cell line by IL‐17 via activation of p38 MAPK, ERK, PI3K/Akt, and NF‐κB pathways

“…Acinar and ductal cell loss, observed in salivary glands from patients with Sjögren's syndrome, is associated with increased salivary gland concentrations of cytokines, including IL‐17 and IL‐6 . The HSG cell line of intercalated ductal cell origin has so far been used to investigate a variety of physiological and pathological status in salivary gland.…”

“…Acinar and ductal cell loss, observed in salivary glands from patients with Sjögren's syndrome, is associated with increased salivary gland concentrations of cytokines, including IL-17 and IL-6. 5,7,11,16 The HSG cell line of intercalated ductal cell origin has so far been used to investigate a variety of physiological and pathological status in salivary gland. They served, for example, as a model to study the effects of inflammatory cytokines on the ductal epithelial cells and decipher mechanisms underlying the SS.…”