Subcutaneous adipose tissue exerts proinflammatory cytokines after minimal trauma in humans

Abstract

Inflammatory cytokines released from adipose tissue play an important role in different pathological processes. In the present study, we investigated the inflammatory cytokine response of human subcutaneous adipose tissue (SAT) by applying the open-flow microperfusion technique. Four standard 18-gauge microperfusion catheters were inserted into periumbilical SAT of eight healthy male volunteers [29 Ϯ 3 yr, BMI 24.3 Ϯ 1.9 (mean Ϯ SD)]. SAT probe effluents were collected at 60-min intervals for 8 h after catheter insertion. Different perfusion fluids were used to measure the local effect of insulin and/or glucose on the cytokine response. SAT probe effluents were analyzed for IL-1␤, IL-6, CXCL8 (IL-8), and TNF-␣. SAT concentrations of IL-1␤ increased 100-fold from 1.0 Ϯ 0.2 pg/ml (mean Ϯ SE) to 101.5 Ϯ 23.2 pg/ml (P Ͻ 0.001) after 8 h. A 130-fold increase was observed for CXCL8, from 49 Ϯ 29 to 6,554 Ϯ 1,713 pg/ml (P Ͻ 0.001). Furthermore, a 20-fold increase of IL-6 was observed within the first 5 h (from 159 Ϯ 123 to 3,554 Ϯ 394 pg/ml; P Ͻ 0.001), and a significant decline to 2,154 Ϯ 216 pg/ml (P Ͻ 0.01) was seen thereafter. Finally, TNF-␣ increased from 1.4 Ϯ 0.6 to 2.5 Ϯ 0.5 pg/ml (P Ͻ 0.05) in hour 2 and remained stable thereafter. Local administration of insulin exerted a stimulatory effect on the inflammatory response of IL-6. In conclusion, SAT exerts a highly reproducible and consistent proinflammatory cytokine response after minimally invasive trauma caused by the insertion of a catheter in humans.

Severe Septal Panniculitis in a Multiple Sclerosis Patient Treated with Interferon-Beta

“…The release of inflammatory cytokines from subcutaneous adipose tissue even after minimal trauma, as also proved in our case by the positivity of TNF-(1 staining, mainly in, the infiltrated inflammatory cells in damaged tissues, may play a role in the inflammatory response (24). Also, the positivity for TNF-(1 correlated with an intense signal immunolocalization for I-CAM1, in accordance with previous studies, showing that TNF-(1 induces the upregulation of ICAM-l (25,26).…”

“…Moreover,authorsunderlinetherole ofintradermal injection as possible trigger of the adverse immune reaction, suggesting deep cutaneous penetration of the drug to avoid these reactions; in fact, the use of adequate training and/or automated injection devices has .been associated with an estimated 60% rate of reduction in the incidence of adverse cutaneous side effects (12,17,24,28).…”

“…Certainly, discontinuation of the drug is followed by a rapid recrudescence of the disease, so education of MS patients regarding the correct administration of DMTs is mandatory in daily management of this invalidating condition (24,28). At the same time, physicians should be familiar with these lesions for prompt diagnosis and treatment of both cutaneous and neurological diseases.…”

Adipose tissue, inflammation and cardiovascular disease

“…Weight loss induced by very low-caloric diet reduces IL-6 levels and improves insulin sensitivity in obese subjects (39) . IL-6 concentrations in subcutaneous adipose tissue are increased by local insulin infusion (40) . At cellular level, IL-6 has demonstrated that it exerts inhibitory effects on gene transcription of IRS-1, GLUT-4, and peroxisome proliferator-activated receptor gamma (PPAR-gamma).…”

“…TNF-α and IL-6 are both secreted by adipocytes, although only IL-6 seems to be released from adipose tissue to the systemic circulation (44) . The concentrations of TNF-α, IL-6, IL-1beta and IL-8 in adipose tissue seem to be unrelated to their systemic concentrations, acting more likely as paracrine mediators (40,44) . Adiponectin is a protein secreted by adipocytes which retains significant homology with collagen X and VII, as well as with the complement factor C1q (45) .…”