Gender difference in the effects of interleukin-6 on grip strength – a systematic review and meta-analysis

Abstract

BackgroundAging 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.MethodsWe 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.ResultsTwenty 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).ConclusionThis 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.Electronic supplementary materialThe online version of this article (10.1186/s12877-018-0798-z) contains supplementary material, which is available to authorized users.

Inflammaging phenotype in rhesus macaques is associated with a decline in epithelial barrier-protective functions and increased pro-inflammatory function in CD161-expressing cells

“…Among the pro-inflammatory cytokines evaluated, IL-12p70, TNF-a, and IL-6 were most notably different between the young and old groups of macaques in our study. IL-6 has emerged as one of the most consistent pro-inflammatory markers associated with age-related degenerative diseases (Forsey et al 2003;Wei et al 1992), with higher plasma levels correlating with sarcopenia in mixed gender populations as well as separately in older men and women (Miko et al 2018). Similarly, increased TNF-α production in blood cells of centenarians and octogenarians with atherosclerosis has been associated with mortality in the elderly population (Bruunsgaard et al 2003;McNerlan et al 2002).…”

Apitherapy for Age-Related Skeletal Muscle Dysfunction (Sarcopenia): A Review on the Effects of Royal Jelly, Propolis, and Bee Pollen

“…Propolis treatment of undifferentiated L6 myoblast selectively stimulated IL-6 production and inhibited pathological cytokines such as interleukin (IL)-1β and TNF-α [ 108 ]. This interesting in vitro investigation indicates that propolis can mimic the mechanism through which exercise induces skeletal muscle remodeling [ 23 , 114 ]. Evidence from preclinical studies shows that concurrent treatment of rats on endurance training with royal jelly enhanced mitochondrial adaptation in muscles that combine both type I and type II fibers such as the soleus muscle whereas neither royal jelly alone nor exercise alone could influence the activity of mitochondrial enzymes in that muscle [ 106 ].…”

“…Similarly, serum and muscle levels of IL-6 temporarily increase following physical exercise, and IL-6 blocks the activity of catabolic cytokines such as TNF-α. On the other hand, chronic inflammation in muscle cells, which correlates with persistent mitochondrial dysfunction and metabolic dysregulation, pathologically activates muscle fiber transformation and atrophy, eventually resulting in the development of sarcopenia [ 23 , 114 ]. It seems that bee products also act dually in skeletal muscle: they support the activity of cytokines that promote muscle remodeling [ 108 ] and suppress muscle-consuming cytokines [ 38 , 101 , 108 ].…”

The association of the serum levels of myostatin, follistatin, and interleukin-6 with sarcopenia, and their impacts on survival in patients with hepatocellular carcinoma

“…44,45 According to a recent meta-analysis, the serum levels for IL-6 correlates negatively with muscle strength in healthy elderly populations. 46 Moreover, many studies have consistently reported that IL-6 has an important effect on the development of sarcopenia and cachexia and promoting tumor growth and metastasis in cancer patients including HCC. In this study, the serum levels of IL-6 showed a significant negative correlation with the Figure 4.…”