Immune-inflammatory pathways and clinical changes in fibromyalgia patients treated with Mindfulness-Based Stress Reduction (MBSR): A randomized, controlled clinical trial.

Fibromyalgia (FM) is a highly prevalent and disabling syndrome characterized by chronic widespread musculoskeletal pain and a broad range of cognitive and affective symptoms. Up to now, the pathogenesis of FM is unknown although a peripheral and central sensitization involving an imbalance on immune biomarkers appears to have a relevant role in its aetiology. The aim of this study was to extend previous clinical findings of Mindfulness-Based Stress Reduction (MBSR) to both its impact on clinical symptomatology and immune biomarkers (IL-6, CXCL8, IL-10 and hs-CRP), and also to explore the role of biomarkers as predictors of efficacy. METHODS: A total of 70 female patients with FM were randomly assigned to two treatment modalities, namely Treatment as Usual (TAU) plus MBSR (n = 35) or TAU alone (n = 35). This study is embedded within a larger RCT (n = 225) that includes three study arms (TAU; TAU plus MBSR; and TAU plus the psychoeducative intervention FibroQoL), and a 12-month follow-up (clinical trial registration: NCT02561416). Blood cytokine assays and clinical assessment were conducted at baseline and post-treatment. Treatment effects were analysed using linear mixed models with intention to treat and per protocol analyses. In order to evaluate the balance between pro- and anti-inflammatory pathways, ratios of pro-inflammatory IL-6, CXCL8 and hs-CRP with the anti-inflammatory cytokine IL-10 were calculated (i.e. IL-6/IL-10, CXCL8/IL10 and hs-CRP/IL-10). RESULTS: The results show that MBSR is an efficacious intervention to reduce clinical severity of patients with FM. MBSR also prevents the tendency of IL-10 to decrease as observed in the TAU group. Higher levels of baseline CXCL8 levels attenuate the beneficial effect of MBSR practice on clinical symptomatology, including pain, energy, stiffness or quality of sleep. Furthermore, higher baseline IL-6/IL-10 and CXCL8/IL-10 ratios were associated with less improvement in psychological inflexibility following MBSR treatment. DISCUSSION: Our results show that mindfulness training has clinical efficacy in patients with FM. The results suggest that MBSR has significant immune regulatory effects in FM patients, while immune-inflammatory pathways may in part predict the clinical efficacy of MBSR. These cytokines and chemokines may be adequate biomarkers to monitor responsivity to MBSR.

Inhibition of angiogenesis in rats by IL-1 receptor antagonist and selected cytokine antibodies.

Daily administration of 50 ng recombinant human interleukin 1-alpha (IL-1 alpha), 25 ng IL-8, 50 ng tumor necrosis factor-alpha (TNF-alpha), or 100 ng basic fibroblast growth factor (bFGF) caused intense neovascularization in a rat sponge model. These cytokine-induced neovascular responses were inhibited by coadministration of IL-1 receptor antagonist (IL-1ra; 50 micrograms), IL-8 antiserum (IL-8-AS; 1: 1000), TNF-alpha antibody (TNF-AB; 500 ng), or a monoclonal antibody to bFGF (DG2; 1000 ng), respectively. These data suggest that it is possible to manipulate the angiogenic response elicited by a defined cytokine by its receptor antagonist or neutralizing antibody. In the absence of exogenous cytokines, the sponge-induced angiogenesis was profoundly suppressed by dexamethasone (5 micrograms/day), but not modified by IL-1ra, IL-8-AS, TNF-AB, and DG2 alone. However, the combination of these four reagents was able to inhibit the sponge-induced neovascular response almost completely. These findings provide direct evidence that IL-1 alpha, IL-8, TNF-alpha and/or bFGF have an intrinsic role in angiogenesis. Further work is necessary to characterize the profile of these cytokines during angiogenesis and to elucidate the nature of their interactions.

Effects of continuous positive airway pressure therapy on systemic inflammation in obstructive sleep apnea: a meta-analysis.

OBJECTIVES: Our meta-analysis was performed to estimate the effect of continuous positive airway pressure (CPAP) therapy on systemic inflammation in patients with obstructive sleep apnea (OSA). METHODS: A comprehensive literature search of PubMed and EMBASE was performed for literature published up to January 2013. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy. RESULTS: A total of 35 studies involving 1985 OSA patients were included in the meta-analysis. Each study investigated one or more inflammatory markers: 24 studies on C-reactive protein (CRP), 16 studies on IL-6, 3 studies on IL-8, and 12 studies on tumor necrosis factor α (TNF-α). The results showed that the SMD (95% confidence interval [CI]) for CRP, IL-6, IL-8, and TNF-α were 0.452 (95% CI, 0.252-0.651), 0.299 (95% CI, 0.001-0.596), 0.645 (95% CI, 0.362-0.929), and 0.478 (95% CI, 0.219-0.736) in pre- and post-CPAP therapy, respectively. The subgroup analyses seemed to support better benefits with therapy duration of ≥3 months and more adequate compliance (≥4 h/night). CONCLUSIONS: CPAP therapy could partially suppress systemic inflammation in OSA patients, and substantial differences were present among the various inflammatory markers.

Roles of IL-8 in ocular inflammations: a review.

INTRODUCTION: This review presents the current in vitro and in vivo animal and human research on the roles of IL-8 in ocular inflammatory diseases. MATERIALS AND METHODS: Data sources were a literature review using Pub Med, Medline, and ISI databases (from 1990 to 2011). Search items included interleukine-8 (IL-8), CXCL8, chemokines, cytokines, alone or in combination with the, serum, aqueous, vitreous, eye, ocular, ocular tissues, ophthalmic, and review. RESULTS: IL-8 may be involved in primary or secondary ocular inflammations. Ocular effects of IL-8 differ based on the source of the secretion and site of the action. The most important effects of IL-8 in the eyes are angiogenic activities and induction of ocular inflammation. CONCLUSION: IL-8 plays important roles in ocular inflammation and angiogenesis in conjunctiva, cornea, iris, retina, and orbit. Anti-IL-8 targeted immunotherapy has been introduced as an important treatment modality, provided that IL-8 signal blocking takes place in desired areas and tissues.

Lactobacillus rhamnosus could inhibit Porphyromonas gingivalis derived CXCL8 attenuation

ABSTRACT An increasing body of evidence suggests that the use of probiotic bacteria is a promising intervention approach for the treatment of inflammatory diseases with a polymicrobial etiology. P. gingivalis has been noted to have a different way of interacting with the innate immune response of the host compared to other pathogenic bacteria, which is a recognized feature that inhibits CXCL8 expression. Objective The aim of the study was to determine if P. gingivalis infection modulates the inflammatory response of gingival stromal stem cells (G-MSSCs), including the release of CXCL8, and the expression of TLRs and if immunomodulatory L. rhamnosus ATCC9595 could prevent CXCL8 inhibition in experimental inflammation. Material and Methods G-MSSCs were pretreated with L. rhamnosus ATCC9595 and then stimulated with P. gingivalis ATCC33277. CXCL8 and IL-10 levels were investigated with ELISA and the TLR-4 and 2 were determined through flow cytometer analysis. Results CXCL8 was suppressed by P. gingivalis and L. rhamnosus ATCC9595, whereas incubation with both strains did not abolish CXCL8. L. rhamnosus ATCC9595 scaled down the expression of TLR4 and induced TLR2 expression when exposed to P. gingivalis stimulation (p<0.01). Conclusions These findings provide evidence that L. rhamnosus ATCC9595 can modulate the inflammatory signals and could introduce P. gingivalis to immune systems by inducing CXCL8 secretion.