As weight gain appears to be a side-effect of inhibitors of IL-6 signaling, they may be a potential pharmacological adjunct for the treatment of cancer cachexia and anorexia nervosa. the IL-6 pathway is usually involved in weight regulation. Modulating IL-6 signaling may be a potential future therapeutic avenue used as an adjunct for the treatment of disorders associated with weight changes, such as cancer cachexia and anorexia nervosa. = 0016, 95% CI [0.03, 0.14]; see Physique 1). The significant between study heterogeneity (I2 = 4.06%, Q = 16.20, = 0.04) was further explored using meta-regressions. The meta-regression explained all heterogeneity (Qmoderators = 12.91, = 0.0048), leaving no significant, unexplained residual heterogeneity (Qresidual = 2.57, = 0.46). The following moderators were included in the final model: diagnosis, time to follow-up, gender and age. The main drivers of between study heterogeneity were a diagnosis of rheumatoid arthritis and age, such that younger patients with rheumatoid arthritis gained more weight. No significant publication bias was uncovered by Beggs rank correlation for funnel plot asymmetry ( = 1.73, = 0.08). Open in a separate window Physique 1 Forest plot of standardized mean change in body weight from nine datasets (= 1531). Zero indicates no effect, whereas points to the right indicate an increase in weight when comparing baseline with follow-up values post-treatment with an IL-6 signaling pathway inhibitor. Pyronaridine Tetraphosphate 2.2.2. Effect of IL-6 Signaling Pathway Inhibitors on BMINine studies were subjected to a BMI meta-analysis (one study was removed as it was shown to be an influential outlier using Cooks distance ), which revealed that patients BMI was significantly increased at follow-up after IL-6 signaling pathway inhibitor commencement (SMCC = 0.10, z = 3.86, = 0001, 95% CI Pyronaridine Tetraphosphate [0.049, 0.15]; see Figure 2). There was no significance between study Pyronaridine Tetraphosphate heterogeneity (I2 = 0%, Q = 8.87, = 0.35). Pooling the mean BMIs of these studies gave a mean baseline BMI of 26.4 kg/m2 and a mean post-treatment BMI of 27.1 kg/m2. Significant publication bias was uncovered by Beggs rank correlation for funnel plot asymmetry ( = 2.15, = 0.03). Open in a separate window Physique 2 Forest plot of standardized mean change in body mass index (BMI) from nine datasets (= 1537). Zero indicates no effect, whereas points to the right indicate an increase in weight when comparing values at baseline and after treatment with an IL-6 signaling pathway inhibitor. 3. Discussion 3.1. Summary of the Main Findings This systematic review and meta-analysis summarize the existing data on the effects of IL-6 signaling pathway inhibitors Rabbit Polyclonal to MC5R on weight and BMI. The results from the meta-analysis show that IL-6 pathway inhibitors were associated with increases in weight and BMI. Pyronaridine Tetraphosphate This pattern of weight gain during treatment with an IL-6 pathway inhibitor is usually in line with research implicating elevated concentrations of IL-6 in the development of cachexia as seen in clinical populations [9,36,37,38,39]. However, it must be considered that, particularly in the case of rheumatoid arthritis where some patients experience weight loss, a restoration of normal body weight may be due to an improvement in disease activity and a reduction in inflammation, rather than a direct effect of the IL-6 signaling pathway inhibitors. 3.2. Possible Mechanisms of IL-6-Induced Weight Loss IL-6 is usually a functionally pleiotropic cytokine implicated in inflammation and infection responses as well as the regulation of metabolic and neural processes. It Pyronaridine Tetraphosphate has many cell-type specific effects and although primarily regarded as a pro-inflammatory cytokine, IL-6 also has many regenerative or anti-inflammatory properties. Given its wide variety of actions IL-6 has been implicated in many aspects of (patho)physiology, including weight and/or fat mass changes. Research thus far points towards a dual role of IL-6 in the central.