Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy

Abstract

The aim was to investigate the levels of cytokines and soluble IL-6R in the tears of patients with thyroid-associated orbitopathy (TAO) disease. Schirmer’s test was adopted to collect tears from TAO patients (N = 20, 17 women, mean age (±SD): 46.0 years (±13.4)) and healthy subjects (N = 18, 10 women, 45.4 years (±18.7)). Lacrimal cytokines and soluble IL-6R (sIL-6R) were measured using a 10-plex panel (Meso Scale Discovery Company) and Invitrogen Human sIL-6R Elisa kit, respectively. Tear levels of IL-10, IL-12p70, IL-13, IL-6 and TNF-α appeared significantly higher in TAO patients than in healthy subjects. Interestingly, IL-10, IL-12p70 and IL-8 levels increased in tears whatever the form of TAO whereas IL-13, IL-6 and TNF-α levels were significantly elevated in inflammatory TAO patients, meaning with a clinical score activity (CAS) ≥ 3, compared to controls. Furthermore, only 3 cytokines were strongly positively correlated with CAS (IL-13 Spearman coeff. r: 0.703, p = 0.0005; IL-6 r: 0.553, p = 0.011; IL-8 r: 0.618, p = 0.004, respectively). Finally, tobacco use disturbed the levels of several cytokines, especially in patient suffering of TAO. The differential profile of lacrimal cytokines could be useful for the diagnosis of TAO patients. Nevertheless, the tobacco use of these patients should be taken into account in the interpretation of the cytokine levels.

Review of Biomarkers in Ocular Matrices: Challenges and Opportunities

“…Clinical studies have reported that tears of dry eye patients show increased levels of IL-1α and mature IL-1β which correlated to corneal fluorescein staining ( 42 , 48 , 65 ). Similar increased levels of inflammatory cytokines have also been reported in active TAO patients indicating that measurement of tear cytokine levels might be a useful diagnostic tool in multiple ocular inflammatory conditions ( 54 , 55 ).…”

“…Many of the same studies and other groups have also shown elevated levels of tumor necrosis factor-alpha (TNF-α) which is thought to represent a measure of the general inflammatory status of the ocular surface in sub-sets of DED ( 48 , 51 , 58 ). TNF-α has also been shown to be significantly higher in tears from TAO patients when compared to controls ( 54 , 55 ). The proinflammatory cytokine Interleukin-1 (IL-1) which includes two forms- Interleukin-1alpha (IL-1α) and Interleukin-1beta (IL-1β) has been detected in human tear fluid ( 39 , 64 ).…”

“…Cytokines and chemokines are endogenous inflammatory mediators secreted by a wide variety of cells and their presence in normal tears have been described ( 39 – 41 ). Multiple studies have demonstrated that various inflammatory and immune-related cytokines/chemokines are significantly increased in tears in DED, SS, ocular allergy, OGVHD and other inflammatory conditions ( 7 , 31 , 42 – 55 ). In addition to the cytokines and chemokines, additional biomarkers have been proposed in ocular allergy to evaluate extent of neutrophil, eosinophil and lymphocyte infiltration by measuring tear fluid levels of IgE, tryptase, histamine and eosinophilic cationic protein (ECP) ( 25 ).…”

Novel Approaches for Immunosuppression in Graves’ Hyperthyroidism and Associated Orbitopathy

“…Rationale and Mechanisms of Action. The level of tumor necrosis factor alpha (TNFα) was found to be elevated in the serum [51], tears [52], and orbital tissues [53] of GO patients compared to controls. TNFα stimulated the expression of adhesion molecules and hyaluronan production in orbital fibroblasts, but these actions were inhibited by anti-TNFα agents [54].…”

“…Higher serum levels of IL-6 were noted in GD patients with GO than in those without GO [73]. Greater lacrimal levels of IL-6 were also shown in GO patients compared to healthy controls, and they positively correlated with CAS [52,74]. Therefore, blocking the IL-6 pathway by tocilizumab (TCZ), a fully human IgG1 anti-IL-6 receptor monoclonal antibody, represents a sound strategy in GO.…”