The online version of this article (https://doi.org/10.1186/s12877-018-0798-z) contains supplementary material, which is available to authorized users.
Aging sarcopenia characterized by low muscle mass with low muscle strength affects men and women differently. The contribution of interleukin-6 (IL-6) to sarcopenia has been suggested based on a negative correlation between plasma IL-6 and muscle function described by some studies. However, no consensus regarding clinically relevant cut-off criteria has been reached. Another question arises whether pooling male and female data is an accurate way to determine the predictive value of IL-6 in sarcopenia. The present meta-analysis was designed to assess: (1) whether plasma IL-6 in aged populations in fact correlates negatively to muscle strength; (2) whether such a correlation exists both in men and in women; and (3) whether plasma IL-6 shows a gender difference in old age.
We applied the preferred reporting items for systematic review and meta-analysis protocols (PRISMA). We searched PubMed and Embase for papers that reported data on individuals over 65 without inflammatory diseases. We extracted either separate male and female data on plasma IL-6 along with at least one muscle parameter or correlation coefficient between plasma IL-6 and these parameters. Random effect models calculated with DerSimonian and Laird weighting methods were applied to analyze correlation coefficients and gender difference in plasma IL-6. Egger’s test was used to assess the small study effect.
Twenty articles out of 468 records identified were suitable for analyses. Plasma IL-6 correlates negatively with grip strength in mixed populations and also separately in men [− 0.25 with 95% confidence interval (CI): − 0.48, − 0.02] and in women (− 0.14 with 95% CI: − 0.24, − 0.03). However, contrary to expectations, men with better muscle condition have higher plasma IL-6 than women of similar age with worse muscle condition (plasma IL-6 male–female difference: 0.25 pg/mL with 95% CI: 0.15, 0.35).
This is the first study to demonstrate that a higher predictive IL-6 cut-off level should be determined for aging sarcopenia in men than in women.
Additional file 1: Literature search strategy. (DOCX 14 kb)12877_2018_798_MOESM1_ESM.docx
Additional file 2: Description of the studies included in the meta-analysis (n = 20). (DOCX 22 kb)12877_2018_798_MOESM2_ESM.docx
Additional file 3: Quality assessment of the papers (observational studies) included based on guidelines from the STROBE statement. (DOCX 16 kb)12877_2018_798_MOESM3_ESM.docx
Additional file 4: Funnel plot of standard error using Fisher’s z. The asymmetrical funnel plot represents the small study effect with regard to Fisher’s z values derived from correlation coefficients. (TIF 40 kb)12877_2018_798_MOESM4_ESM.tif
Additional file 5: Forest plot representing the male minus female differences in mean age of corresponding groups from the same studies. Squares show the difference in mean values with the grey area reflecting the weight assigned to the study. Horizontal bars indicate 95% confidence intervals (95% CI). The diamond shows the overall effect size (ES) with the corresponding 95% CI. Subgroups in Ogawa et al.  are indicated with Arabic numerals. A lack of age difference was found: ES = 0.14 with 95% CI (− 0.11, 0.39) p = 0.265. The heterogeneity of the data was low: p = 0.195, I2 = 25.3%. No small study effect was identified using Egger’s test: p = 0.487. (TIF 156 kb)
Additional file 6: Forest plot representing the male minus female standardized differences in mean values of various muscle parameters (muscle mass/strength/function) in corresponding groups from the same studies. Squares show the difference in mean values with the grey area reflecting the weight assigned to the study. Horizontal bars indicate 95% confidence intervals (95% CI). The diamond shows the overall effect size (ES) with the corresponding 95% CI. Subgroups in Ogawa et al.  are indicated with Arabic numerals. A: Grip strength; B: Chair stand test; C: 6-min walk; D: Lean mass; E: Up and go test; F: Muscle volume; G: Fat-free mass; H: Knee extension test; I: Thigh muscle area. Significantly higher muscle mass/strength/function was demonstrated in male than in female volunteers (i.e. positive standardized difference in mean values): ES = 1.82 with 95% CI (1.62, 2.02) p < 0.001. The heterogeneity of the data was high: p < 0.001, I2 = 95.4%. No small study effect was identified using Egger’s test: p = 0.163. (TIF 295 kb)
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