TNF-α, IFN-γ, IL-10, and IL-4 levels were elevated in a murine model of human sickle cell anemia maintained on a high protein/calorie diet

Abstract

Increased frequency and risk of infection is one of the well described complications of sickle cell anemia (SCA). Dietary supplementation in children with SCA and growth retardation improved growth and decreased incidence of infection. We investigated the impact of a high protein diet on weight gain, hematological profile, and immune cytokine levels in the Berkeley model of SCA, 16 of which were randomized to either regular mouse diet with 20% of calories from protein (n = 8) or a test feed with 35% of calories from protein (n = 8). Control mice (C57BL/6, n = 16) were correspondingly randomized, and were all feed ad libitum for three months with actual intake estimated by subtracting the weight of gnaw waste from that of the feed given. Blood was collected at sacrifice by cardiac puncture and plasma levels of T helper cell 1 (TH1) and TH2 associated cytokines were measured using a multiplex antibody immobilized bead assay. SCA mice receiving the 35% protein diet had modest improvements in weight, red blood cell count, and hemoglobin level, with a slight decrease in reticulocyte count compared with SCA mice on the regular mouse diet. Furthermore, they also had significantly higher plasma levels of cytokines tumor necrosis factor (TNF)-α (P = 0.02), interferon (IFN)-γ (P = 0.01), interleukin 10 (IL-10; P = 0.02), and IL-4 (P = 0.02) compared with those that received the 20% protein diet. We conclude that providing additional protein calories to transgenic SCA mice increased the plasma levels of acute inflammatory cytokines associated with immune response to infection, which might partly explain decreased episodes of infection observed among supplemented children with SCA.

Peripheral blood mononuclear cells as a source to detect markers of homeostatic alterations caused by the intake of diets with an unbalanced macronutrient composition

“…The increase in cytokine signaling in PBMCs is in accordance to increased TNF-alpha serum levels in the animals. This supports the notion that increased protein intake has been related to an increase in plasma levels of acute inflammatory cytokines [47]. A chronic immune-enhancement may underlie problems like metabolic syndrome [48][49][50], and our data indeed suggest that care should to be taken when using HP diets.…”

Precipitating factors and targeted therapies in combating the perils of sickle cell disease--- A special nutritional consideration

“…Supplementation of high protein diet resulted in decreased infection which can provide a clue to decreasing the incidents of infection in children with SCA. An increase in TNF -α, TNF- γ, IL-10, and IL-4 cytokines has been noted in the murine model of human SCA which is alleviated by supplementing a high protein diet [ 26 ]. In another study, decreased levels of CRP and IL-6 are observed on feeding a high protein diet [ 27 ].…”

Body composition and grip strength are improved in transgenic sickle mice fed a high-protein diet

“…After 3 months on the diets, mean age range for the groups (C mice fed the diet supplying 20 % energy from protein (C20), C mice fed the diet supplying 35 % energy from protein (C35), S mice fed the diet supplying 20 % energy from protein (S20), S mice fed the diet supplying 35 % energy from protein (S35)) was 118–120 d. The typical characteristics of the S v. C mice, wherein S mice have lower Hb and higher reticulocyte and leucocyte counts, were seen and are mentioned elsewhere ( 34 ) . As expected, weight increased for all groups after 3 months of feeding (Fig.…”