Seasonal redistribution of immune function in a migrant shorebird: annual-cycle effects override adjustments to thermal regime.

Throughout the annual cycle, demands on competing physiological systems change, and animals must allocate resources to maximize fitness. Immune function is one such system and is important for survival. Yet detailed empirical data tracking immune function over the entire annual cycle are lacking for most wild animals. We measured constitutive immune indices once a month for a year on captive red knots (Calidris canutus). We also examined temperature as an environmental contributor to immune variation by manipulating ambient temperature to vary energy expenditure. To identify relationships among immune indices, we performed principal-component analysis. We found significant repeatability in immune indices over the annual cycle and covariation of immune indices within and among individuals. This covariation suggests immune strategies as individual traits among individuals and the use of different immune strategies during different annual-cycle stages within individuals. Over the annual cycle, both higher-cost phagocyte-based immunity and lower-cost lymphocyte-based immunity were high during mass change, but there was a clear shift toward lower-cost lymphocyte-based immunity during peak molt. Experimental manipulation of temperature had little effect on annual variation in immune function. This suggests that other environmental factors, such as food availability and disease, should also be examined in the future.

Tariquidar, a selective P-glycoprotein inhibitor, does not potentiate loperamide's opioid brain effects in humans despite full inhibition of lymphocyte P-glycoprotein.

BACKGROUND: Loperamide, a potent opioid, has been used as an in vivo probe to assess P-glycoprotein activity at the blood-brain barrier, because P-glycoprotein inhibition allows loperamide to cross the blood-brain barrier and exert its central opioid effects. In humans, studies with nonselective and moderately potent inhibitors resulted in mild opioid effects but were confounded by the concurrent inhibition of loperamide's metabolism. The authors studied the effect of the highly selective, potent P-glycoprotein inhibitor tariquidar on loperamide's central opioid effects. METHODS: In a randomized, double-blind, crossover study, nine healthy subjects received on 2 study days oral loperamide (32 mg) followed by an intravenous infusion of either tariquidar (150 mg) or placebo. Central opioid effects (pupil diameter, sedation) were measured for 12 h, and blood samples were drawn up to 48 h after drug administration to determine plasma loperamide concentrations and ex vivo P-glycoprotein activity in T lymphocytes. Values for pupil diameter and loperamide concentrations were plotted over time, and the areas under the curves on the tariquidar and placebo study day were compared within each subject. RESULTS: Tariquidar did not significantly affect loperamide's central effects (median reduction in pupil diameter area under the curve, 6.9% [interquartile range, -1.4 to 12.1%]; P = 0.11) or plasma loperamide concentrations (P = 0.12) but profoundly inhibited P-glycoprotein in lymphocytes by 93.7% (95% confidence interval, 92.0-95.3%). CONCLUSION: These results suggest that despite full inhibition of lymphocyte P-glycoprotein, the selective P-glycoprotein inhibitor tariquidar does not potentiate loperamide's opioid brain effects in humans.

A decrease of plasma macrophage migration inhibitory factor concentration is associated with lower numbers of circulating lymphocytes in experimental Plasmodium falciparum malaria.

Macrophage migration inhibitory factor (MIF) has recently been implicated in the pathogenesis of malarial anaemia. However, field studies have reported contradictory results on circulating MIF concentrations in patients with clinically overt Plasmodium falciparum malaria. We determined plasma MIF levels over time in 10 healthy volunteers during experimental P. falciparum infection. Under fully controlled conditions, MIF levels decreased significantly during early blood-stage infection and reached a nadir at day 8 post-infection. A decrease in the number of circulating lymphocytes, which are an important source of MIF production, paralleled the decrease in MIF levels. Monocyte/macrophage counts remained unchanged. At MIF nadir, the anti-inflammatory cytokine interleukin (IL)-10, which is an inhibitor of T-cell MIF production, was detectable in only 2 of 10 volunteers. Plasma concentrations of the pro-inflammatory cytokines IL-8 and IL-1beta were only marginally elevated. We conclude that circulating MIF levels decrease early in blood-stage malaria as a result of the decline in circulating lymphocytes.

Study of Cbl-b dynamics in peripheral blood lymphocytes isolated from patients with multiple sclerosis.

E3 ubiquitin ligase Casitas B cell lymphoma-b (Cbl-b) has been recently highlighted as a negative regulator of T-cell activation and which dysfunction usually results in autoimmunity. To present, however, the possible involvement of Cbl-b in multiple sclerosis (MS), an autoimmune demyelinating disease mediated by T-helper 1 (Th1) cells is still unclear. To clarify this, using reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analyses, we thus investigated the levels of Cbl-b mRNA and protein in peripheral blood T-lymphocytes isolated from 11 MS patients in acute relapse phase and 20 cases in remission phase. 16 healthy subjects were used as normal control. Cbl-b mRNA and protein levels were found both significantly down-regulated in peripheral blood lymphocytes isolated from MS patients (P<0.0001). Interestingly, this decrease of Cbl-b protein but not mRNA levels was significantly more marked in samples of relapsed patients than that of remitted cases (P<0.0001). In addition, it was shown that Cbl-b mRNA levels being inversely correlated with the frequency of MS clinical relapses (P<0.0001). Altogether, the data show for the first time that Cbl-b dynamics in peripheral blood T-lymphocyte subset and which possible relationship with the clinical onsets during MS.

Sphingosine-1-phosphate analogue FTY720 causes lymphocyte redistribution and hypercholesterolemia in ApoE-deficient mice.

OBJECTIVE: Resident immune cells are a hallmark of atherosclerotic lesions. The sphingolipid analogue drug FTY720 mediates retrafficking of immune cells and inhibits their homing to inflammatory sites. We have evaluated the effect of FTY720 on atherogenesis and lipid metabolism. METHODS AND RESULTS: ApoE-/- mice on a normal laboratory diet received oral FTY720 for 12 weeks, which led to a 2.4-fold increase in serum cholesterol (largely VLDL fraction) and a 1.8-fold increase in hepatic HMGCoA reductase mRNA. FTY720 increased plasma sphingosine-1-phosphate and induced marked peripheral blood lymphopenia. A discoordinate modulation of B, T and monocyte cell numbers was found in peripheral lymphoid organs. Overall depletion of T cells was accompanied by a relative (2-fold) increase in regulatory T cell content paralleled by a similar increase in effector memory T cells (CD4+ CD44hi CD62lo) as absolute numbers of both subpopulations remained essentially unchanged. Lymphocyte function was unaltered as indicated by anti-OxLDL antibodies and T cell proliferation. There were no changes in atherosclerotic lesions in early and established atherosclerosis. CONCLUSIONS: FTY720 mediated peripheral lymphocyte depletion and retrafficking without altering function and overall balance of pro- and antiatherogenic lymphocyte populations. A net decrease in lymphocyte numbers occurred concomitantly with a more proatherogenic hypercholesterolemia resulting in unaltered atherogenesis.

Crotoxin alters lymphocyte distribution in rats: Involvement of adhesion molecules and lipoxygenase-derived mediators.

Crotoxin is the main neurotoxic component of Crotalus durissus terrificus snake venom and modulates immune and inflammatory responses, interfering with the activity of leukocytes. In the present work, the effects of crotoxin on the number of blood and lymphatic leukocytes and on lymph nodes and spleen lymphocytes population were investigated. The toxin s.c. administered to male Wistar rats, decreases the number of lymphocytes in blood and lymph circulation and increases the content of B and T-lymphocytes in lymph nodes. These effects were detected 1-2h after treatment. The crotoxin molecule is composed of two subunits, an acidic non-toxic polypeptide, named crotapotin and a toxic basic phospholipase A(2) (PLA(2)). PLA(2), but not crotapotin, decreased the number of circulating blood and lymph lymphocytes. Crotoxin promotes leukocyte adherence to endothelial cells of blood microcirculation and to lymph node high endothelial venules, which might contribute to the drop in the number of circulating lymphocytes. Crotoxin increases expression of the adhesion molecule LFA-1 in lymphocytes. The changes in the expression of the adhesion molecule might contribute, at least in part, for the increased leukocyte adhesion to endothelium. Zileuton, a 5-lipoxygenase inhibitor, blocked the decrease in the number of circulating leukocytes induced by crotoxin and also abolished the changes observed in leukocyte-endothelial interactions, suggesting the involvement of lipoxygenase-derived mediators in the effects of the toxin.

Genome instability is increased in lymphocytes of women with polycystic ovary syndrome and is correlated with insulin resistance.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and reproductive and metabolic abnormalities. The potential genetic contributors to PCOS are unclear. We tested the hypothesis that genomic instability (chromosome malsegregation and DNA damage) is increased in PCOS. METHODS: Overweight age, weight and BMI-matched women with (n=14) and without (n=16) PCOS (age 34.2+/-6.0 years, weight 90.7+/-14.5 kg, BMI 34.0+/-5.6 kg/m(2), mean+/-S.D.) were assessed for chromosome malsegregation (assessed by X chromosome chromogenic in situ hybridisation) and micronucleus frequency (assessed by the cytokinesis block micronucleus index) in lymphocytes. RESULTS: Women with PCOS had significantly elevated genomic instability as demonstrated by a significantly higher number of binucleated lymphocytes containing micronuclei, total number of micronuclei, a higher proportion of aneuploid X chromosome signals (2:1 X and 3:1 X) and a lower proportion of normal X chromosome segregation signals (2:2 X) in binucleated lymphocytes than women without PCOS. Surrogate measures of insulin resistance positively correlated with the proportion of aneuploid cells (2:1; 3:1 X chromosome signals) and inversely with the proportion of normal cells (2:2 X chromosome signals). CONCLUSION: Women with PCOS display increased genomic instability (higher micronuclei and chromosome malsegregation) compared to women without PCOS and this increase may be related to the insulin resistance phenotype.

Immunological cell and serum metabolite response of 60-week-old commercial laying hens to an alfalfa meal molt diet.

The practice of induced molting involves the restriction of light, feed removal and optionally water for 5-14 days. However, there is growing concern regarding feed removal and animal welfare issues. With this in mind, alternative diets have been developed to produce similar molting effects as that of feed deprivation. Alfalfa, which largely consists of insoluble fiber, can be used as a molting diet. In this study, heterophil and lymphocyte counts, serum chemistry, and organ weight parameters were evaluated in hens that were deprived of feed or fed alfalfa during a nine day induced molt. Full-fed hens were used as the control. Blood serum parameters assessed included calcium, magnesium, glucose, total protein, ketone bodies, uric acid, and cholesterol. White blood cells were counted and categorized by cell type. On the ninth day of the trial, the hens were euthanized and the liver, spleen, heart, intestine, pancreas, ovary, oviduct, and kidney were collected and weighed. On day 8 birds molted with alfalfa or by feed deprivation had significantly higher (P<0.05) levels of ketone bodies and cholesterol and lower levels of calcium, and magnesium compared to the full-fed hens while birds molted by feed deprivation exhibited significantly lower levels of uric acid. Birds molted by both methods exhibited significant reductions in ovary, oviduct, liver and pancreas weights and increased spleen weights when compared to the non-molted hens. On days 0, 2, and 6 there were no significant differences (P>0.05) in either heterophil or lymphocyte percentages. However, heterophil percentages were higher in feed withdrawal birds than full-fed birds on day 4 but lymphocyte percentages were higher in full-fed birds compared to feed withdrawal birds. On day 8 of the induced molt lymphocyte percentages were higher from full-fed birds when compared to feed withdrawal birds but no significant differences were detectable for heterophil percentages. Based on reproductive organ weight loss and changes in serum and immunological responses of birds during molt, it appears that alfalfa meal can be an effective molt induction alternative.

The relationship between measures of nutritional status and masticatory function in untreated patients with head and neck cancer.

PURPOSE: Nearly 40% of newly diagnosed patients with head and neck cancer are malnourished before treatment begins with many researchers ascribing the malnutrition to a paucity of teeth. We attempted to determine if inadequate numbers of occluding pairs of teeth, rather than mere numbers of teeth, in newly hospitalized, untreated head and neck cancer patients correlates with nutritional status parameters used to identify those at heightened risk for malnutrition-related complications. PATIENTS AND METHODS: Patients and cancer-free, matched controls were evaluated for malnutrition (body mass index < or = 20 [weight (kg)/height (m2)]), serum albumin < or = 2.7 g/dL, hemoglobin < or = 11.9 g/dL, and total lymphocyte count < or = 1,449/muL), and inadequate numbers of occluding pairs of teeth variably defined as less than 5 "posterior pairs" of occluding teeth or less than 6 or 7 "total pairs" of occluding teeth. RESULTS: Head and neck cancer patients had significantly lower body mass index (P = .005) and total lymphocyte count (P = .019) than controls, but there were no significant correlations between the nutritional and dental variables in either group. CONCLUSIONS: Untreated head and neck cancer patients frequently have nutritional status parameters indicating heightened risk for malnutrition-related complications but inadequate masticatory function is not a causative factor.

Influence of prenatal psychosocial stress on cytokine production in adult women.

The aim of the present study was to determine the association between prenatal stress and immune function in human adults. Peripheral blood mononuclear cells (PBMCs) from 34 healthy young women whose mothers experienced major negative life events during their pregnancy (Prenatal Stress, PS group, mean age 25, SD +/- 4.34 years), and from a female comparison group (n = 28, CG, mean age 24 +/- 3.40 years), were stimulated with phytohemagglutinin (PHA), and subsequent cytokine production was measured. A bias for T-helper 2 (Th2) cytokine production due to an overproduction of IL-4 relative to IFN-gamma after PHA stimulation was observed in PS subjects. In addition, IL-6 and IL-10 were also significantly elevated. To the best of our knowledge, this study is the first to suggest a direct association between prenatal stress exposure and alterations in immune parameters in adult women.

Propagation of a transmissible cytotoxic activity on cultures of human peripheral blood lymphocytes.

Positive results were attained when human peripheral blood lymphocytes (PBLs) were investigated for their ability to propagate a transmissible cytotoxic activity (TCA) isolated on VERO cell cultures from a sample of cerebrospinal fluid (CSF) drawn from a woman with ischemic brain injury. In consideration of this finding it can be assumed that "in vivo" blood lymphocytes contributed to give rise to the TCA detected "in vitro" in the CSF inoculum.

Flow cytometric analysis of canine umbilical cord blood lymphocytes.

Lymphocyte subsets in canine umbilical cord blood were flow cytometrically analyzed and compared with those of the dams' peripheral blood. The proportion of CD3+ T lymphocytes, CD21+CD3- B lymphocytes, and CD3-CD21- non-T non-B lymphocytes in umbilical cord blood was 52.9%, 30.4%, and 16.7%, respectively. T lymphocyte/B lymphocyte ratio was significantly lower in the umbilical cord blood than in the dams' peripheral blood (2.1 +/- 1.4 versus 11.0 +/- 8.1, P < 0.001). In contrast, CD4+ lymphocyte/CD8+ lymphocyte ratio was significantly higher in the umbilical cord blood than in the dams' peripheral blood (7.6 +/- 2.2 versus 1.8 +/- 0.6, P<0.001). These findings clarified the phenotypic characters of canine umbilical cord blood lymphocytes.

Neuroendocrine and immune responses to 16-day bed rest with realistic launch and landing G profiles.

BACKGROUND: Spaceflight is associated with increased glucocorticoids and catecholamines, both well-known for their immunosuppressive effects. The objective of this study was to develop a model of spaceflight by using a human centrifuge to reproduce launch and landing G forces along with bed rest to simulate microgravity. HYPOTHESIS: Acute changes in G forces are causal factors in neuroendocrine and immune changes. METHODS: Ten subjects underwent realistic launch G-force profiles followed by 16 d of 60 head-down tilt bed rest. At the end of the bed rest, subjects were subjected to realistic landing G-force profiles. Stress hormones and changes in leukocyte and lymphocyte subsets were measured in blood and urine samples over the course of the study. RESULTS: Similar to shorter Shuttle missions (i.e., < or = 9 d), plasma cortisol was significantly decreased at simulated landing while urinary epinephrine was significantly increased. Urinary cortisol was significantly increased after simulated launch. The pattern of leukocyte and lymphocyte changes also mirrored the changes found in shorter 9-d spaceflights. CONCLUSIONS: These data suggest a role for both catecholamines and glucocorticoids in mediating changes in leukocyte and lymphocyte subsets during simulated microgravity coupled with hypergravity. Our results were also strikingly similar to those from actual Shuttle missions and support our conclusion that we have developed a model of spaceflight.

The effect of antiepileptic drugs administered in pregnancy on micronucleus frequency in cord blood lymphocytes.

OBJECTIVES: Epidemiological data indicate that the pregnancies of epileptic women constitute about 1% of all pregnancies. A large group of antiepileptic drugs (AEDs) applied in long-term monotherapy or polytherapy produce toxic metabolites as well as free radicals and reactive oxygen species. The aim of this study was to assess the potential genotoxic effect of AED therapy in pregnancy on DNA structure of umbilical cord blood lymphocytes. MATERIAL AND METHODS: The study group were 30 newborns (14 males and 16 females) of mothers receiving long-term AED therapy during pregnancy. The AED considered were carbamazepine, valproic acid, phenyltriazine, benzodiazepine, gamma-aminobutyric acid and sulfonamide analogues. The controls were infants born to mothers not exposed to any medication in pregnancy (n = 20). Positive controls were the same infants, but in this case Nitrogranulogen (Sigma) was added to the collected cord blood samples (n = 11). Micronucleus (MN) assay was used as an indicator of chromosome damage. The frequency (%) of MN/1000 binucleated cells and the nuclear division index (NDI) were calculated. RESULTS: Mean MN frequency and NDI were respectively 0.110 (+/-0.152), 1.592 (+/-0.206) in the study group and 0.050 (+/-0.061), 1.628 (+/-0.178) in the controls (statistically non-significant difference, p > 0.1). CONCLUSION: The findings did not reveal any genotoxic effect or inhibition of nuclear division in cord blood lymphocytes by AED metabolites. This was reflected by the absence of significant between-group differences in the mean MN frequency and NDI.

[Immunity features in patients with upper respiratory tract disease caused by Chlamydia].

Comparative analysis of results of clinical and laboratory evaluation of patients with chronic nasal or nasal sinuses' diseases (chronic rhinitis or maxillary sinusitis) associated or not associated with Chlamydia infection was performed. It was shown that in patients infected with Chlamydia, along with unidirectional changes typical for all patients irrespective from presence or absence of Chlamydia, the features of immune response against these infectious agents take place.

Lymphocyte numbers and subsets in the human blood. Do they mirror the situation in all organs?

Lymphocyte numbers in the blood are used to evaluate the immune status on a daily basis in medicine. Several studies have documented the normal ranges of lymphocytes and lymphocyte subsets in the peripheral blood. A variety of techniques and criteria have revealed clear differences between the lymphocyte subsets in childhood and adolescence. Race and gender are also variables for blood lymphocytes, and even environmental factors seem to influence the numbers of some lymphocyte populations. However, do all these variations in lymphocyte subsets in the peripheral blood mirror changes in the lymphocyte populations of the whole body, or is it just a result of different migratory habits of cells? The factors influencing the distribution of lymphocytes in the peripheral blood with regard to the different abilities of T and B cells to migrate to distinct lymphoid or non-lymphoid tissue are summarized. In addition it will be described how the removal of organs (e.g. thymus, spleen, liver) influences the distribution of lymphocytes in the blood. All these parameters should be considered not only in the clinical situation when the immune status of a patient is extrapolated from the lymphocyte numbers in the blood, but also when interpreting treatment effects in patients.

Effect of an immune-enhancing diet on lymphocyte in head-injured rats: what is the role of arginine?

OBJECTIVE: The benefit of immune-enhancing diets (IEDs) in the intensive care unit remains controversial. Considering their complexity, the role of each component, in particular arginine (Arg), in their properties is largely unknown. The aim of this study was to determine the role of arginine in the immunomodulatory effects of an IED (Crucial) in head-injured rats. DESIGN: Thirty-four rats were randomized into five groups: AL (ad libitum), HI (head-injured), HI-STD (HI + standard enteral nutrition, EN), HI-STD-Arg (HI + standard EN + Arg in equimolar concentration to Arg in IED), and HI-IED (HI + IED). These isocaloric and isonitrogenous diets were administered over 4 days. After death, the thymus was removed and weighed. The density of CD25, CD4 and CD8 on lymphocytes from blood and from Peyer patches was evaluated. Mesenteric lymph nodes, liver and spleen were cultured for analysis of enterobacterial translocation and dissemination. MEASUREMENTS AND RESULTS: HI induced an atrophy of the thymus which was not corrected by the standard diet (HI 0.27 +/- 0.03, HI-STD 0.35 +/- 0.03 vs. AL 0.49 +/- 0.02 g; p < 0.05). However, the standard diet supplemented with arginine limited the thymic atrophy and the IED restored thymus weight. CD25 density and interleukin-2 production were increased only in the HI-STD-Arg and HI-IED groups (p < 0.05). Head injury induced enterobacterial translocation and dissemination which were blunted only in the HI-STD-Arg group (p < 0.05). CONCLUSIONS: In this rat HI model, arginine appears to be safe, contributes to a large extent to the immunomodulatory effects of the IED, and seems to limit enterobacterial translocation and dissemination more efficiently alone than in an IED.

Low frequency and low intensity pulsed electromagnetic field exerts its antiinflammatory effect through restoration of plasma membrane calcium ATPase activity.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting 1% of the population worldwide. Pulsed electromagnetic field (PEMF) has a number of well-documented physiological effects on cells and tissues including antiinflammatory effect. This study aims to explore the antiinflammatory effect of PEMF and its possible mechanism of action in amelioration of adjuvant induced arthritis (AIA). Arthritis was induced by a single intradermal injection of heat killed Mycobacterium tuberculosis at a concentration of 500 microg in 0.1 ml of paraffin oil into the right hind paw of rats. The arthritic animals showed a biphasic response regarding changes in the paw edema volume. During the chronic phase of the disease, arthritic animals showed an elevated level of lipid peroxides and depletion of antioxidant enzymes with significant radiological and histological changes. Besides, plasma membrane Ca(2+) ATPase (PMCA) activity was inhibited while intracellular Ca(2+) level as well as prostaglandin E(2) levels was noticed to be elevated in blood lymphocytes of arthritic rats. Exposure of arthritic rats to PEMF at 5 Hzx4 microT x 90 min, produced significant antiexudative effect resulting in the restoration of the altered parameters. The antiinflammatory effect could be partially mediated through the stabilizing action of PEMF on membranes as reflected by the restoration of PMCA and intracellular Ca(2+) levels in blood lymphocytes subsequently inhibiting PGE(2) biosynthesis. The results of this study indicated that PEMF could be developed as a potential therapy for RA in human beings.

gamma-H2AX foci formation in peripheral blood lymphocytes of tumor patients after local radiotherapy to different sites of the body: dependence on the dose-distribution, irradiated site and time from start of treatment.

PURPOSE: To evaluate the relationship between an estimated integral total body radiation dose delivered and phosphorylated histone H2AX protein (gamma-H2AX) foci formation in peripheral blood lymphocytes of cancer patients. MATERIAL AND METHODS: gamma-H2AX formation was quantified as the mean number of foci per lymphocyte (N(meanH2AX)) and the percentage of lymphocytes with > or =n foci. The integrated total body radiation dose was estimated from the dose volume histogram of patient's body corrected for the proportion of the body scanned by computed tomography for 3D treatment planning. RESULTS: There was a strong linear correlation between the mean number of gamma-H2AX foci per lymphocyte in the peripheral blood sample and integrated total body radiation dose (r = 0.83, p < 0.0001). The slope of the relationship was dependent on the site of body irradiated. In comparison to chest irradiation with a slope of 8.7 +/- 0.8 foci Gy(-1), the slopes for brain, upper leg and pelvic sites were significantly shallower by -4.7, -4.3, and -3.8 Gy(-1), respectively (p < 0.0001), while the slope for upper abdomen irradiation was significantly larger by 9.1 +/- 2.6 Gy(-1) (p = 0.0007). There was a slight time effect since the start of radiotherapy on the slopes of the in vivo dose responses leading to shallower slopes (-1.5 +/- 0.7 Gy(-1), p = 0.03) later (> or =10 day) during radiotherapy. After in vitro irradiation, lymphocytes showed 10.41 +/- 0.12 foci per Gy with no evidence of inter-individual heterogeneity. CONCLUSIONS: gamma-H2AX measurements in peripheral lymphocytes after local radiotherapy allow the estimation of the applied integral body dose. The site and time dependence have to be considered.

Influence of G308A polymorphism of tumor necrosis factor-alpha gene on inflammatory markers in postsurgical head and neck cancer patients with early enteral nutrition.

OBJECTIVE: Although immune dysfunction in patients with cancer could be multifactorial, the immune system may be modulated by nutritional substrates and genetic background. Our study evaluated the effect of G308A polymorphism of the tumor necrosis factor-alpha (TNF-alpha) gene on inflammatory markers in patients after surgery for head and neck cancer who received early enteral nutrition. METHODS: A population of 60 patients with oral and laryngeal cancer was enrolled. At surgery patients were treated with a hyperproteic enteral diet. Perioperatively and on postoperative day 6 the following parameters were evaluated: serum values of prealbumin, transferrin, total number of lymphocytes, interleukin-6, TNF-alpha, and C-reactive protein. In addition, genotyping of G308A gene polymorphism was assessed. RESULTS: Patients' mean age was 61.1 +/- 14.6 y (four women, 56 men) with a body mass index of 25.4 +/- 5.2 kg/m(2) and a previous weight loss of 0.35 +/- 0.2 kg. Forty patients (37 men, 3 women; 66.6%) had the genotype G308/G308 (wild group) and 20 patients (19 men, 1 woman; 23.4%) had the genotype G308/A308 (mutant group). A significant increase in prealbumin and transferrin levels was detected in both groups. C-reactive protein decreased in both groups (wild group: 105.1 +/- 60 versus 53.8 +/- 62.3 mg/dL, P < 0.05; mutant group: 99.5 +/- 46 versus 43.9 +/- 51.9 mg/dL, P < 0.05). Interleukin-6 decreased in both groups (wild group: 20.1 +/- 22 versus 6.2 +/- 4.1 pg/mL, P < 0.05; mutant group: 22.3 +/- 38 versus 9.2 +/- 7.4 pg/mL, P = NS). Lymphocytes increased in both groups (wild group: 1102 +/- 468 versus 1600 +/- 537 10(3)/mL, P = NS; mutant group: 1441 +/- 739 10(3)/mL versus 1669 +/- 614 10(6)/mL, P = NS). TNF-alpha showed no changes. CONCLUSION: The G308A polymorphism of the TNF-alpha gene did not affect levels of inflammatory markers in patients after surgery for head and neck cancer who were treated with early enteral nutrition.