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The TGF-β superfamily has been shown to play an important role in a wide range of physiological as well as pathological processes including ageing, immune modulation, atherosclerosis and cancer development. The aim of the current study was to investigate (i) whether TGF-β signalling in peripheral blood mononuclear cells (PBMCs) would differ between young and old females and (ii) whether physical performance parameters of elderly women would be related to the expression of TGF-β or its receptors. Sixteen healthy young (22-28 years; YF) and 90 healthy older (65-92 years; OF) females participated in the study. In addition to several components of health-related physical fitness, circulating CRP and TGF-β levels were determined together with the mRNA expression of TGF-β, TGF-βRI, TGF-βRII, and miRNA-21 (known to interfere with TGF-β signalling) in PBMCs. Physical fitness as determined by 6-minutes walking test (YF:median 932 (range 573-1254) m; OF:360 (114-558) m), handgrip strength (YF: 32 (24-39) kg; OF:18(10-30) kg), relative isokinetic peak torque of knee extensors (YF:1.9 (1.2- 2.3) Nm/kg; OF:1.0 (0.2-1.9) Nm/kg and flexors (YF: 1.1 (0.7- 1.5) Nm/kg; OF: 0.5 (0.2-1.0) Nm/kg was substantially lower in older women (p<0.001 for all comparisons). These changes were paralleled by an increase in hs-CRP (YF: 0.9 (0.1-4.3)mg/L; OF: 2.3 (0.3-56.7)mg/L,p<0.001). Serum levels of TGF-β and TGF-β mRNA levels from PBMCs did not differ between young and old women whereas, both TGF- βRI/GAPDH (YF: 4.07 (1.38-14.60); OF: 2.08 (0.14-28.81); p=0.020) and TGF-βRII/GAPDH levels (YF: 3.16 (1.14- 10.25); OF: 1.71 (0.51-14.86); p=0.020) were lower with respect to old age. In elderly women, only TGF-βRΙ expression correlated negatively with miRNA-21 expression in PBMCs (ρ=-0.315; p=0.004). Interestingly, hs-CRP and miRNA correlated positively with handgrip strength (ρ=0.237 and ρ=243, p<0.05), while none of the TGF-β-related parameters were related to physical performance. The results suggest that age affects TGF-β signalling in leukocytes by altering the expression levels of its receptors. These changes seem to occur independently of physical fitness of old women., (Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.)

With the discovery of microRNAs (miRNAs), an exceptional means of regulating gene expression was introduced a few years ago. MiRNAs function to inactivate specific messenger RNA transcripts leading to depletion of the corresponding protein, whereby computational studies have shown that about one third of all animal genes might be miRNA targets. Recent publications highlight the involvement of miRNAs in regulating the immune response. The aim of this review is to provide an overview of miRNA biogenesis and function, to illustrate their impact on both the innate as well as the adaptive immune system, to show the regulation of skeletal muscle plasticity and inflammation, and finally to present their possible role within the field of exercise immunology.

Prolonged or repeated stimulation of Toll-like receptor (TLR) 4 leads to hyporesponsiveness of monocyte-derived macrophages, which seems to be a hallmark of immunosuppression related to sepsis and cancer. Two negative regulators of TLR-4 signaling are IL-1 receptor-associated kinase M and B-cell leukemia 3. Here, we demonstrate that the expression of both proteins is inhibited when the TLR-7/TLR-8 agonist CL097 is added to monocyte cultures despite costimulation with the TLR-4 agonist LPS or hyaluronic acid. Reduction of IL-1 receptor-associated kinase M and B-cell leukemia 3 was paralleled by a significant increased cytokine induction of TNF-alpha, IL-10, and IL-12 observed after intracellular and extracellular TLR stimulation. In ex vivo stimulated whole blood of patients who have prolonged sepsis or metastatic cancer, TLR-7/TLR-8 agonists retained their ability of increased stimulation of TNF-alpha. These data might add to the understanding of sepsis and cancer-associated immune suppression in men.

Multiple trauma patients have an impaired immune system and thus frequently develop life-threatening septic complications. Because there is an ongoing debate on which are the most predictive immunologic parameters of clinical outcome, we prospectively studied 19 multiple trauma patients with sepsis (mean age, 38.7 +/- 15.8 years; mean Injury Severity Score, 40.6 +/- 11.6) over a period of 14 days. The following parameters were measured daily after admission to the intensive care unit: ex vivo lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production, monocyte human leukocyte antigen (HLA)-DR expression, constitutive interleukin (IL) 6 secretion, white blood cell count, and C-reactive protein. In addition, procalcitonin, neopterin, LPS-binding protein, and constitutive TNF-alpha secretion were measured every third day. Immediately after trauma, all patients had significantly lower levels of HLA-DR and ex vivo LPS-stimulated TNF-alpha secretion than healthy controls (n = 7; P < 0.001). On the day after clinical diagnosis of sepsis, before any other parameter differed between survivors (n = 13) and nonsurvivors (n = 6), ex vivo LPS-induced TNF-alpha secretion was significantly lower (P < 0.05) in nonsurvivors than in survivors. We conclude that ex vivo LPS-induced TNF-alpha production is an earlier predictor of clinical outcome in multiple trauma patients with sepsis than monocyte HLA-DR expression, constitutive IL-6 secretion, or any other parameter assessed.