High Vitreous Concentration of IL-6 and IL-8, but Not of Adhesion Molecules in Relation to Plasma Concentrations in Proliferative Diabetic Retinopathy

Abstract

Background/Aim: Inflammatory markers have been observed in proliferative diabetic retinopathy (PDR). We assessed vitreous concentrations of adhesion molecules and cytokines in PDR and non-diabetic controls and plasma concentrations to differentiate local inflammation from the breakdown of the blood-retina barrier. Methods: 38 patients with PDR and 16 controls with macular hole or epiretinal membrane underwent vitrectomy. Vitreous and plasma soluble adhesion molecules [sE-selectin, intercellular adhesion molecule (sICAM)-1 and -3, platelet-endothelial cell adhesion molecule (sPECAM)-1, sP-selectin, vascular cell adhesion molecule (sVCAM)-1] and cytokines [interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 (p70), tumour necrosis factor-α and -β, γ-interferon] were detected by the multiplex assay. Results: Levels of IL-6 and IL-8 were 26-fold (p = 0.001) and 6-fold higher (p = 0.001) in vitreous than in plasma in PDR. Vitreous IL-10 (p = 0.004), sPECAM-1, sE-selectin, sICAM-1 and sVCAM-1 were higher in PDR than controls (p = 0.001 for all). Adhesion molecule concentrations in vitreous in PDR were less than 10% of those in plasma. IL-10 was lower in vitreous than plasma (3.0 vs. 12.8 pg/ml, p = 0.007), and the vitreous IL-10/IL-8 ratio was significantly lower in PDR than in controls (0.10 vs. 0.55 pg/ml, p = 0.003). Conclusion: The elevated IL-6 and IL-8 levels in vitreous, but not in plasma, are evidence favouring local over systemic inflammation in PDR. Furthermore, there was imbalance between inflammatory and anti-inflammatory cytokines in the vitreous.

Serum concentrations of selected chemokines (CXCL1/GROα and CXCL8/IL8) in patients with type 1 diabetes

“…Badacze z ośrodka poznańskiego wykazali, że chemokina CXCL8/IL8 ulega zmianom w zależności od wyrównania metabolicznego u pacjentów zarówno z T1DM, jak i T2DM cukrzycy [17]. Inni badacze wykryli zwiększone stężenie białka CXCL8/ IL8 w ciele szklistym pacjentów z objawami retinopatii cukrzycowej [27][28]. W badanich Koskela et al (2013) wykazano 6-krotnie wyższe stężenie CXCL8/IL8 w ciele szklistym niż w surowicy u pacjentów z T1DM oraz PDR [28].…”

“…Inni badacze wykryli zwiększone stężenie białka CXCL8/ IL8 w ciele szklistym pacjentów z objawami retinopatii cukrzycowej [27][28]. W badanich Koskela et al (2013) wykazano 6-krotnie wyższe stężenie CXCL8/IL8 w ciele szklistym niż w surowicy u pacjentów z T1DM oraz PDR [28].…”

Determinants of microvascular function in individuals with and without type 2 diabetes

“…Possibly, the difference in arterial stiffness between individuals without and with (pre)diabetes was too small in this relatively well-treated population 71 . Last, inflammatory markers drawn from venous plasma, as compared to local measurement, may have underestimated the contribution of the low-grade inflammation index on (pre)diabetes-associated microvascular endothelial dysfunction 72 . From chapter 2 and 3 it follows that hyperglycemia itself, rather than the cardiovascular risk context in which diabetes typically develops, is the main contributor to the differences in retinal and skin microvascular function between individuals with prediabetes or relatively well-controlled T2D and individuals with normal glucose metabolism (NGM).…”

“…As these diseases, which are (in part) of microvascular origin, affect both individuals with and without T2D, it is important to elucidate determinants of microvascular endothelial function in the general population. Several small (mostly intervention) studies 55,[68][69][70][71][72][73][74] have investigated major cardiovascular risk factors as determinants of microvascular function. These cardiovascular risk factors included (directly) modifiable factors (e.g.…”

“…aging and male sex). However, these studies 55,[68][69][70][71][72][73][74] were conducted with small numbers of highly selected individuals. For example, study populations were comprised of lean versus obese subjects with a body mass index of 21 kg/m 2 versus 39 kg/m 2 68 , or compared highly trained professional football players with untrained individuals 74 , which is not representative for habitual physical activity.…”