Associations Between Dietary Fat Intake, Pain, and Interleukin-10 Levels in Adults with Steady-State Sickle Cell Disease
Li Yang, Stephanie Wildridge, Ashley Buscetta, Siobhan M Lawler, Samuel M Degenhard, Djaina-Shae Dervil, Danetta Hooks, Shanna Yang, Sara Turner, Allison Brichacek, Rebecca Metellus, Vence M Bonham, Nicole FarmerAbstract
Background
Interleukin-10 (IL-10) is a pleiotropic cytokine with potent immunosuppressive properties that inhibit the expression of inflammatory genes. In sickle cell disease (SCD), vaso-occlusive crisis (VOC) is a major clinical complication driven in part by dysregulation of pro- and anti-inflammatory pathways. Studies have shown that individuals with SCD in steady state have higher circulating IL-10 levels compared with those experiencing VOC. IL-10 suppresses the production of multiple pro-inflammatory cytokines and immune cell function, potentially acting in response to the inflammatory milieu in sickle cell disease. Associations between IL-10 levels and several dietary factors, including fiber, fructose, vitamin D, and total fat intake, as well as specific fat subtypes such as saturated (SFA), polyunsaturated (PUFA), and monounsaturated fatty acids (MUFA) have been identified in prior research in adults without SCD. Nutrition studies, to date, in individuals living with SCD have not directly reported on associations with nutrient intake, diet quality, and IL-10 levels.
Methods
The Diet and SCD Study is an observational mixed-methods study initiated in 2022 with a target sample of 80 adults living with SCD in the United States. The purpose of the study is to evaluate associations between dietary intake and disease severity among non-hospitalized U.S. adults (age≥18 years of age) with a confirmed diagnosis of SCD, and presence of steady-state symptoms for at least 4 weeks. The study has a hybrid design of in-person and telehealth procedures. The study data collected include clinical assessment, electronic surveys on patient-reported outcomes, and laboratory variables, including SCD disease-specific markers. For this analysis, data from two unannounced phone-administered 24-hour recall interviews were used to determine dietary intake and specific nutrient quantity was determined by use of Nutrition Data System for Research software. Cytokine levels were measured using a multiplex immunoassay. Spearman’s correlation coefficients were determined to measure associations using SPSS version 29.
Results
Among the study sample with a quantifiable level of IL-10 (n = 44), participants were predominantly female (72.7%), with a mean age of 42.3 years (± 11.9). Just over half were seen through in-person visit (52.3%), most had SCD genotype SS (65.9 %), and the median annual income was $60,000-69,000. The mean BMI (n = 30) was 25.0 kg/m2 (±5.2), and the mean disease severity score was 14.4 (± 4.11), corresponding to moderate disease severity. Mean IL-10 concentration was 6.3 ± 3.5 pg/ml. Greater pain frequency over the prior 12 months was positively related to IL-10 (ρ = 0.386, p = 0.010). Average daily nutrient intakes were 17.8 ± 9.41 g of fiber, 20.9 ± 15.6 g of fructose, 5.6 ± 7.26 µg of vitamin D, 77.7 ± 34.5 g of fat, and 1,853.8 ± 757.65 kcal of total energy. Higher intake of omega-3 fatty acids (ρ = −0.388, p = 0.009), beta-tocopherol (ρ = −0.312, p = 0.039), gamma-tocopherol (ρ = −0.370, p = 0.013), delta-tocopherol (ρ = −0.350, p = 0.020), and percent calories from polyunsaturated fat (ρ = −0.363, p = 0.015) were associated with lower IL-10 levels, whereas higher percent calories from saturated fat was associated with higher IL-10 levels (ρ = 0.312, p = 0.039). Stratified subgroup analyses were conducted by IL-10 median levels. Significant inverse associations only remained for delta-tocopherol (ρ=-.484, p = 0.022) and calories from polyunsaturated fat (ρ=-.611, p = 0.003) within the lower range of IL-10 levels, suggesting that for these nutrients there is a difference in the relationship with IL-10 depending on the cytokine level.
Conclusions
Among adults with SCD in steady state, higher intake of omega-3 fatty acids, certain forms of vitamin E, and greater adherence to healthy fat intake patterns were correlated with lower IL-10 levels, whereas higher saturated fat intake was associated with elevated IL-10 levels. These findings suggest that in the presence of certain nutrients that may impact inflammation, there may not be a need for an IL-10 adaptive response, or individuals with lower IL-10 levels may have higher intake of dietary nutrients that can similarly influence inflammation. Future inclusion of direct measurement of IL-10 levels in nutrition supplementation and nutrient studies in SCD research is needed to provide further insight on this topic.