Anorexia is part of the body's acute-phase response to illness. Microbial products such as lipopolysaccharides (LPS), which are also commonly used to model acute illness, trigger the acute-phase response and cause anorexia mainly through pro-inflammatory cytokines. LPS stimulate cytokine production through the cell-surface structural molecule CD14 and toll-like receptor-4. Cytokines ultimately change neural activity in brain areas controlling food intake and energy balance. The blood–brain barrier endothelial cells (BBB EC) are an important site of cytokine action in this context. BBB EC and perivascular cells (microglia and macrophages) form a complex regulatory interface that modulates neuronal activity by the release of messengers (e.g. PG, NO) in response to peripheral challenges. Serotonergic neurons originating in the raphe nuclei and glucagon-like peptide-1-expressing neurons in the hindbrain may be among the targets of these messengers, because serotonin (5-HT), acting through the 5-HT2C receptor, and glucagon-like peptide-1 have recently emerged as neurochemical mediators of LPS anorexia. The central melanocortin system, which is a downstream target of serotonergic neurons, also appears to be involved in mediation of LPS anorexia. Interestingly, LPS also reduce orexin expression and the activity of orexin neurons in the lateral hypothalamic area of fasted mice. As the eating-stimulatory properties of orexin are apparently related to arousal, the inhibitory effect of LPS on orexin neurons might be involved in LPS-induced inactivity and anorexia. In summary, the immune signalling pathways of LPS-induced, and presumably acute illness-induced, anorexia converge on central neural signalling systems that control food intake and energy balance in healthy individuals.

The present study compared leucine kinetics and acute-phase-protein concentrations in three groups of marasmic, acutely infected Malawian children fed one of three isoenergetic diets. These were: an enhanced-protein-quality diet (egg-white+tryptophan, providing 1.2 g protein/kg per d; n 14); an increased-protein-content diet (egg-white+tryptophan, providing 1·8 g protein/kg per d; n 14); a standard-protein diet (1·2 g milk protein/kg per d; n 25). The hypotheses tested were that children receiving a diet with more protein would have greater rates of non-oxidative leucine disposal and that children receiving an isonitrogenous diet with a higher protein quality would have lower rates of leucine oxidation. The children were studied after 24 h of therapy using standard [13C]leucine stable-isotope tracer techniques. The children receiving the higher-protein-content diet had greater leucine kinetic rates than those receiving the standard-protein-content diet; non-oxidative leucine disposal was 170 (SD 52) v. 122 (SD 30) μmol leucine/kg per h (P<0·01). Leucine oxidation was less in the children receiving the enhanced-protein-quality diet than in those receiving the standard-protein-quality diet; 34 (SD 12) v. 45 (SD 13) μmol leucine/kg per h (P<0·05). The children receiving the high-protein-content diet increased their serum concentration for five of six acute-phase proteins 24 h after starting therapy, while those receiving the standard-protein-content diet did not. These data suggest that there was greater whole-body protein synthesis, and a more vigorous acute-phase response associated with the higher-protein-content diet. The clinical benefits associated with a higher protein intake in marasmic, acutely infected children need further study.

The present experiments were conducted to investigate influences of dietary methionine and cysteine on metabolic responses to immunological stress induced by Escherichia coli lipopolysaccharide (LPS) injection, and concanavalin A (Con A)-induced mononuclear cell (MNC) proliferation in male broiler chickens. In Expt 1, chicks (12 d of age) were fed on a S amino acid (SAA)-deficient diet (5.6 g SAA/kg diet) or on three kinds of SAA-sufficient diet (9.3 g SAA/kg diet; low-, medium- and high-cysteine diets) which contained 2.8, 4.65 and 6.5 g cysteine/kg diet, respectively. Plasma a-1 acid glycoprotein (AGP) concentration and interleukin (IL)-1-like activity in chicks fed on the SAA-deficient diet were lower following a single injection of LPS than those in chicks fed on the SAA-sufficient diets. At 16 h after LPS injection, plasma Fe and Zn concentrations and body weight were reduced, but AGP concentration and IL-1-like activity in plasma were significantly increased. These changes in body weight, plasma Zn and Fe concentrations following injection of LPS were not affected by dietary methionine:cysteine ratios. Plasma AGP concentration and IL-1-like activity in chicks fed on the high-cysteine diet were, however, greater than those in chicks fed on the other diets following a single injection of LPS. In Expt 2, chicks (7 d of age) were fed on the SAA-sufficient diets as in Expt 1 for 10 d. MNC proliferation in spleen induced by Con A in chicks fed on the high-cysteine diet was greater than that in chicks fed on the low- or medium-cysteine diet. The results suggest that dietary cysteine has an impact on the immune and inflammatory responses.

To investigate Fe nutritional indices in malaria infection in children, haematology (blood haemoglobin, plasma ferritin, transferrin, Fe, and transferrin saturation), acute phase markers (albumin and caeruloplasmin) and liver function tests were studied in fifty consecutive cases of severe and mild falciparum malaria, fifty matched controls and twenty-three cases of asymptomatic malaria. Blood haemoglobin and transferrin were lower, while ferritin and transferrin saturation were higher, in groups with symptomatic malaria in comparison with the control group. The differences were greatest with the severest form of the disease. There were no differences between any of the groups in plasma Fe. Plasma transferrin correlated directly with albumin in asymptomatic, mild and severe malaria groups (r 0.48, 0.65 and 0.83; P < 0.05, P < 0.01 and P < 0.001 respectively), and inversely with caeruloplasmin (r −0.65, −0.34 and −0.43; P < 0.01, P < 0.05 and P < 0.01 respectively). For ferritin, the correlation was inverse with albumin (r −0.65, −0.57 and −0.64; P < 0.01, P < 0.001 and P < 0.001 respectively and direct with caeruloplasmin (r 0.83, 0.21 and 0.49, P < 0.001, NS and P < 0.001 respectively). Multiple regression analysis on data from all patients combined indicated that albumin, and to a lesser extent alanine aminotransferase (EC 2.6.1.2) activity, explained 62 % of the variance in transferrin. Caeruloplasmin, parasite count and albumin explained 59 % of the variance in ferritin, and transferrin and unconjugated bilirubin explained 62 % of the variance in Fe values. In conclusion, these data suggest that low transferrin and high ferritin values are primarily due to the acute phase response. High transferrin saturation and lack of differences in plasma Fe between the groups are probably due to Fe released from lysed erythrocytes. Finally, in both symptomatic and asymptomatic malaria, indices of Fe status can be misleading and may be especially problematic in community studies in malaria-endemic areas where asymptomatic malaria may be common.

The present study investigated the effect of the acute-phase ‘injury’ response, induced by subcutaneous injection of turpentine, on the hydration and protein content of organs and tissues of normally nourished rats receiving a diet containing 200g protein/kg, and of protein-malnourished rats receiving a diet containing 30 g protein/kg. The measurements were carried out 48 h after turpentine injection, and were compared with both saline-injected animals, and pair-fed control animals. Circulating α2-macroglobulin was also measured as an index of the acute-phase-protein response. In normally nourished rats turpentine injection caused a significant increase in the mean masses of the liver, kidney and lung (7–35% compared with saline-injected animals, and 20–44% compared with pair-fed controls), and a small reduction in the mass of extra-abdominal and extrathoracic tissues (‘carcass’). In general the protein content of tissues changed in a similar way (for liver, kidney and lung a 16–33% increase compared with saline-injected animals, and 32–49% compared with pair-fed controls). Protein deficiency produced a significant attenuation in the response to turpentine. The change in the mass and protein content of several tissues was reduced (for lung, liver and kidney, the increase in protein content was only 5–15%), and the effects on anorexia (1 v. 41% reduction infood intake) and the α2,-macroglobulin response (1·28 v. 4·28 g/l; P< 0·001) were also reduced. It is concluded that the injury response spares most central thoracic and abdominal organs, but this effect as well as the anorexia and acute-phase-protein response to injury are attenuated by protein deficiency.

The effect of dietary protein concentration on stress responses against injection of Escherichia coli lipopolysaccharide (LPS) was studied in male broiler chickens. Chickens (7 d of age) were fed on a 100 (low-protein; LP) or 300 g protein/kg (high-protein; HP) diet for 2 weeks. LPS was injected intraperitoneally every 2 d during the final 6 d, or once 16 h before the end of the experiment, at a concentration of 900 μg/chick. The LPS injection did not affect body-weight gain, feed intake, gain:intake ratio, or plasma Fe concentration. The single injection of LPS reduced plasma Zn concentration, but the repeated injections did not. Feeding the HP diet increased the response of plasma Zn concentration to the single injection of LPS. Plasma albumin concentration was reduced by LPS injection. Feeding the HP diet resulted in a higher plasma α 1-acid glycoprotein (AGP) concentration than feeding the LP diet, in chicks untreated with LPS. An increase in plasma AGP concentration observed after LPS injection in chicks fed on the LP diet was greater than that seen in chicks fed on the HP diet. No significant changes in plasma AGP concentration in response to repeated injections of LPS were observed in chicks fed on the HP diet. Plasma interleukin-1 (IL-l)-like activity was greater in chicks fed on the LP diet than in those fed on the HP diet, when LPS was injected. The response of plasma IL-1-like activity to the single injection of LPS in chicks fed on the LP diet was the greatest among the treatment groups. These results suggest that acute-phase responses to LPS injection are much greater in chicks fed on a LP diet than in those fed on a HP diet, and multiple injection of LPS weakens the responses.