Introduction Obesity-associated insulin resistance is related to adipose tissue inflammation, characterized by macrophage infiltration and altered adipose tissue remodeling, including adipocyte hypertrophy ( Weisberg et al . 2003 , Xu et al
AnneMarie Gagnon, Charlie Foster, Anne Landry, and Alexander Sorisky
Marina C Muñoz, Jorge F Giani, Marcos A Mayer, Jorge E Toblli, Daniel Turyn, and Fernando P Dominici
of additional serine kinases cannot be ruled out. Obesity and insulin resistance are closely associated with a state of chronic low-grade inflammation characterized by abnormal cytokine production and macrophage infiltration into adipose tissue
J. A. P. Da Silva, S. H. Peers, M. Perretti, and D. A. Willoughby
The influence of gender and sex hormones upon both the hypothalamic-pituitary-adrenal (HPA) axis and the immune and inflammatory responses is well recognized, but it is not clear to what extent the two effects are interdependent. We have investigated this interaction using a chronic inflammation model. Corticosterone levels were measured in mature BALB/c male and female mice, which were intact, sham-operated or gonadectomized. No significant differences were found between groups in baseline corticosterone, but systemic inflammation (cotton-induced granulomas) resulted in stimulation of the HPA axis in a reproducible pattern. Corticosterone levels were higher in sham-operated females than in males, but gonadectomy had opposing effects in the two genders, resulting in reduced levels in females but significantly increased levels in males. A similar pattern emerged after stimulation by ether exposure or injection of interleukin-1β. In the chronic inflammatory model, replacement of ovariectomized females with physiological levels of progesterone restored a response similar to that of intact females. Physiological levels of 5α-dihydrotestosterone prevented the increase in corticosterone levels caused by castration in males and also resulted in reduced corticosterone levels in sham-operated females. Oestradiol treatment did not affect corticosterone levels. Release of interleukin-1 by peritoneal macrophages from intact and gonadectomized mice with chronic inflammation followed a similar pattern, females releasing more than males. These data suggest a complex inter-relationship between sex steroids, inflammatory stimuli and the HPA axis, such that females have a greater tendency than males to generate activating signals and in addition have a greater sensitivity to such factors.
Journal of Endocrinology (1993) 136, 389–397
Vimal Selvaraj and Lan N Tu
adrenals and testes, TSPO is highly abundant. In contrast, TSPO expression in cells of the nervous system is extremely weak ( Daugherty et al . 2013 ), and it is uncertain if upregulation seen during inflammation/injury approaches the levels seen in
SJ Heasman, KM Giles, C Ward, AG Rossi, C Haslett, and I Dransfield
Glucocorticoids represent one of the most effective clinical treatments for a range of inflammatory conditions, including severe acute inflammation. Although glucocorticoids are known to affect processes involved in the initiation of inflammation, the influence of glucocorticoids on the mechanisms by which acute inflammation normally resolves have received less attention. Apoptosis of granulocytes present at inflamed sites leads to their rapid recognition and internalisation by macrophages, a process which may be important for resolution of inflammation. However, if clearance of either eosinophils or neutrophils is impaired, these cells rapidly undergo secondary necrosis leading to release of pro-inflammatory mediators from the phagocyte, potentially prolonging inflammatory responses. Physiologically relevant concentrations of glucocorticoids accelerate eosinophil apoptosis whilst delaying neutrophil apoptosis during in vitro culture. Here we discuss key pathways regulating the granulocyte apoptotic programme and summarise the effects of glucocorticoids on monocyte differentiation and the consequent changes to apoptotic cell clearance capacity. Definition of the mechanisms underlying resolution of inflammatory responses following glucocorticoid treatment may unveil new targets for modulation of inflammatory disease, allowing co-ordinated augmentation of granulocyte apoptosis together with increased macrophage capacity for clearance of apoptotic cells.
RM Gow, MK O'Bryan, BJ Canny, GT Ooi, and MP Hedger
A single intraperitoneal injection of lipopolysaccharide (LPS) causes a biphasic suppression of testicular steroidogenesis in adult rats, with inhibition at 6 h and 18-24 h after injection. The inhibition of steroidogenesis is independent of the reduction in circulating LH that also occurs after LPS treatment, indicating a direct effect of inflammation at the Leydig cell level. The relative contributions to this inhibition by intratesticular versus systemic responses to inflammation, including the adrenal glucocorticoids, was investigated in this study. Adult male Wistar rats (eight/group) received injections of LPS (0.1 mg/kg i.p.), dexamethasone (DEX; 50 microg/kg i.p.), LPS and DEX, or saline only (controls), and were killed 6 h, 18 h and 72 h later. Treatment with LPS stimulated body temperature and serum corticosterone levels measured 6 h later. Administration of DEX had no effect on body temperature, but suppressed serum corticosterone levels. At the dose used in this study, DEX alone had no effect on serum LH or testosterone at any time-point. Expression of mRNA for interleukin-1beta (IL-1beta), the principal inflammatory cytokine, was increased in both testis and liver of LPS-treated rats. Serum LH and testosterone levels were considerably reduced at 6 h and 18 h after LPS treatment, and had not completely recovered by 72 h. At 6 h after injection, DEX inhibited basal IL-1beta expression and the LPS-induced increase of IL-1beta mRNA levels in the liver, but had no effect on IL-1beta in the testis. The effects of DEX on IL-1beta levels in the liver were no longer evident by 18 h. In LPS-treated rats, DEX caused a significant reversal of the inhibition of serum LH and testosterone at 18 h, although not at 6 h or 72 h. Accordingly, DEX inhibited the systemic inflammatory response, but had no direct effect on either testicular steroidogenesis or intra-testicular inflammation, at the dose employed. These data suggest that the inhibition of Leydig cell steroidogenesis at 6 h after LPS injection, which was not prevented by co-administration of DEX, is most likely due to direct actions of LPS at the testicular level. In contrast, the later Leydig cell inhibition (at 18 h) may be attributable to extra-testicular effects of LPS, such as increased circulating inflammatory mediators or the release of endogenous glucocorticoids, that were inhibited by DEX treatment. These data indicate that the early and late phases of Leydig cell inhibition following LPS administration are due to separate mechanisms.
Diane Donegan, Laurie K Bale, and Cheryl A Conover
assays (radioimmunoassay vs ELISA), conditioned media concentrations, and cell type (murine vs human). Although we did not see a direct effect of AGE or high glucose on HMC PAPP-A production, there is accumulating evidence to suggest that inflammation
Mark E Cleasby, Pauline M Jamieson, and Philip J Atherton
metabolite fluxes in the muscle of sarcopenic obese patients is shown in Fig. 2 . Inflammation in obesity and in muscle Obesity is now recognised to be a subclinical inflammatory state characterised by increased infiltration of adipose tissue with
S Otabe, N Wada, T Hashinaga, X Yuan, I Shimokawa, T Fukutani, K Tanaka, T Ohki, S Kakino, Y Kurita, H Nakayama, Y Tajiri, and K Yamada
chronic inflammation, and the possible effects of adiponectin on sirtuin levels. To answer these questions, we established KK/Ta mice expressing human adiponectin in the liver. The KK/Ta mouse is an animal model of metabolic syndrome exhibiting moderate