Abstract
Inflammation is a common adverse event of anti-cancer therapy. Royal jelly (RJ) modulates inflammation by regulating the levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and interleukin (IL)-6 produced by macrophages. Macrophage colony stimulating factor (M-CSF) is a crucial regulator of macrophage activities, and we hypothesized that RJ alters M-CSF levels. In this randomized controlled trial, we investigated the association between M-CSF and adverse events in renal cell carcinoma patients treated with tyrosine kinase inhibitors (TKIs) after an oral intake of RJ (n = 16) or placebo (n = 17). The serum levels of M-CSF, TNF-α, TGF-β, and IL-6 were measured by an enzyme-linked immunosorbent assay, and their temporal changes and correlation between such changes were analyzed. The post-/pretreatment ratio of M-CSF levels was associated with anorexia after 2 weeks and fatigue after 2, 4, and 12 weeks. The M-CSF level in the RJ group was higher than that in the placebo group at the same timepoints. The TNF-α level in the RJ group was lower than that in the placebo group between 6 and 12 weeks, and the TGF-β level in the RJ group was higher than that in the placebo group; however, contrasting findings were detected after 12 weeks. Additionally, the M-CSF level was significantly correlated with the TGF-β level after 4 weeks and IL-6 level after 8 and 10 weeks. Among TNF-α, TGF-β, and IL-6, the post-/pretreatment ratio of TGF-β after 12 weeks was associated with TKI-induced anorexia, and the ratios after 10 and 12 weeks were associated with fatigue. Our results demonstrated that an oral intake of RJ suppressed anorexia and fatigue via complex mechanisms associated with inflammation-related factors, such as M-CSF and TGF-β in renal cell carcinoma patients treated with TKIs. In addition, we newly found that such RJ-related effects were dependent on the treatment duration.
Highlights
Chronic inflammation is closely associated with the pathogenesis of various types of chronic diseases, and many investigators have paid special attention to the preventive effects of a variety of nutraceuticals that regulate disease-related inflammation [1,2]
We previously reported that an oral intake of royal jelly (RJ) suppresses anorexia and fatigue in Renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKIs) [19]
The present study showed that an oral intake of RJ influences serum Macrophage colony stimulating factor (M-CSF) levels in RCC patients treated with TKIs
Summary
Chronic inflammation is closely associated with the pathogenesis of various types of chronic diseases, and many investigators have paid special attention to the preventive effects of a variety of nutraceuticals that regulate disease-related inflammation [1,2]. Numerous investigators have suggested that complex immune responses, regulated by various types of immune cells, Med. Sci. 2020, 8, 43 cytokines, and pro-/anti-inflammatory mediators, play a crucial role in cancer-related inflammation [3,4]. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β are closely associated with several cancer-related symptoms and adverse events of anti-cancer therapy, such as cachexia and fatigue [5,6,7]. Understanding the regulatory mechanisms underlying chronic inflammation is important for the management of anti-cancer therapy-associated unpleasant symptoms experienced by cancer patients
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