Dehydration enhances innate immunity in a semiaquatic snake from the wet-dry tropics.

Dehydration is considered a physiological challenge, and many organisms live in environments that undergo periods of reduced water availability that can lead to dehydration. Recent studies have found a positive relationship between dehydration and innate immune function in animals adapted to xeric or semixeric environments. To explore the generality of this relationship, we examined the impact of dehydration on innate immune performance in water pythons (Liasis fuscus), a semiaquatic snake from the wet-dry tropics of Australia. We collected blood samples from male and female water pythons held in the laboratory without food and water for 4 weeks. We also collected blood from free-ranging snakes throughout the Austral dry-season. We evaluated plasma osmolality and innate immune function (agglutination, lysis, and bacterial-killing ability) and found that increased osmolality, whether manipulated in the laboratory or as a result of natural water limitation, resulted in enhanced aspects of innate immune performance. Counter-intuitively, snakes in the wild became more hydrated as the dry season progressed, suggesting the dehydrated snakes move to water sources periodically to rehydrate. Comparing our data with those from previous studies, we suspect species divergence in the level of dehydration (i.e., hyperosmolality) that triggers enhanced immune capabilities.

Dehydration triggers ecdysone-mediated recognition-protein priming and elevated anti-bacterial immune responses in Drosophila Malpighian tubule renal cells.

BACKGROUND: Drosophila is a powerful model for the study of factors modulating innate immunity. This study examines the effect of water-loss dehydration on innate immune responsiveness in the Drosophila renal system (Malpighian tubules; MTs), and how this leads to elevated host defense and contributes to immunosenescence. RESULTS: A short period of desiccation-elevated peptidoglycan recognition protein-LC (PGRP-LC) expression in MTs, increased antimicrobial peptide (AMP) gene induction, and protected animals from bacterial infection. We show that desiccation increased ecdysone synthesis in MTs, while inhibition of ecdysone synthesis or ecdysone receptor expression, specifically within MTs, prevented induction of PGRP-LC and reduced protection from bacterial infection. Additionally, aged flies are constitutively water-stressed and have elevated levels of ecdysone and PGRP-LC. Conversely, adults aged at high relative humidity show less water loss and have reduced expression of PGRP-LC and AMPs. CONCLUSIONS: The Drosophila renal system is an important contributor to host defense and can modulate immune responses in an organ autonomous manner, responding to environmental changes such as desiccation. Desiccation primes immune responsiveness by elevating PGRP-LC expression specifically in MTs. In response to desiccation, ecdysone is produced in MTs and acts in a paracrine fashion to increase PGRP-LC expression, immune responsiveness, and improve host defense. This activity of the renal system may contribute to the immunosenescence observed in Drosophila.

Probiotics reduce repeated water avoidance stress-induced colonic microinflammation in Wistar rats in a sex-specific manner.

The colonic response to stress is greater in female rats than in male rats. The aim of this study was to evaluate the effect of probiotics in the repeated water avoidance stress (rWAS)-induced colonic microinflammation model of Wistar rats in a sex-specific manner. The three groups (no-stress, WAS, and WAS with probiotics) were exposed to r-WAS for 1 h daily for 10 days, and Lactobacillus farciminis was administered by oral gavage for 10 days to animals in the probiotics group. The visceromotor response (VMR) to colorectal distension (CRD) was assessed using a barostat and noninvasive manometry before and after WAS exposure. Immunohistochemistry for mast cells and real-time polymerase chain reaction (RT-PCR) for detection of mucosal cytokines were performed using distal colon tissue after the animals were sacrificed. Significant reduction of VMR to CRD (visceral analgesia) was observed at 60 mmHg in the female WAS group (P = 0.045), but not in males. In addition, the female WAS with probiotics group showed a significantly lower colonic mucosal mast cell count in comparison to the female WAS group (P = 0.013), but this phenomenon was not observed in the male group. The colonic mucosal mRNA levels of interferon-γ (IFNR), tumor necrosis factor-α (TNFA), interleukin (IL) 6, and IL17 were higher in the female WAS group than in the male WAS group. The mRNA levels of IFNR, TNFA, and IL6 were significantly decreased in WAS females who received probiotics (all P < 0.050). In conclusion, rWAS is induced in a sex-specific manner. A 10-day-long treatment with L. farciminis is an effective therapy for rWAS-induced colonic microinflammation in female rates, but not in male rats.

The influence of hydration status during prolonged endurance exercise on salivary antimicrobial proteins.

PURPOSE: Antimicrobial proteins (AMPs) in saliva including secretory immunoglobulin A (SIgA), lactoferrin (SLac) and lysozyme (SLys) are important in host defence against oral and respiratory infections. This study investigated the effects of hydration status on saliva AMP responses to endurance exercise. METHODS: Using a randomized design, 10 healthy male participants (age 23 ± 4 years, [Formula: see text] 56.8 ± 6.5 ml/kg/min) completed 2 h cycling at 60 % [Formula: see text] in states of euhydration (EH) or dehydration (DH) induced by 24 h fluid restriction. Unstimulated saliva samples were collected before, during, immediately post-exercise and each hour for 3 h recovery. RESULTS: Fluid restriction resulted in a 1.5 ± 0.5 % loss of body mass from baseline and a 4.3 ± 0.7 % loss immediately post-exercise. Pre-exercise urine osmolality was higher in DH than EH and overall, saliva flow rate was reduced in DH compared with EH (p < 0.05). Baseline SIgA secretion rates were not different between conditions; however, exercise induced a significant increase in SIgA concentration in DH (161 ± 134 to 309 ± 271 mg/L) which remained elevated throughout 3 h recovery. SLac secretion rates increased from pre- to post-exercise in both conditions which remained elevated in DH only. Overall, SLac concentrations were higher in DH than EH. Pre-exercise SLys concentrations were lower in DH compared with EH (1.6 ± 2.0 vs. 5.5 ± 6.7 mg/L). Post-exercise SLys concentrations remained elevated in DH but returned to pre-exercise levels by 1 h post-exercise in EH. CONCLUSIONS: Exercise in DH caused a reduction in saliva flow rate yet induced greater secretion rates of SLac and higher concentrations of SIgA and SLys. Thus, DH does not impair saliva AMP responses to endurance exercise.

Global burden of childhood diarrhea and interventions.

PURPOSE OF REVIEW: Diarrhea is a leading cause of morbidity and mortality among children under 5 years in low-income and middle-income countries. Over the past 2 decades under-five mortality has decreased substantially, but reductions have been uneven and unsatisfactory in resource-poor regions. RECENT FINDINGS: There are known interventions which can prevent diarrhea or manage children who suffer from it. Interventions with proven effectiveness at the prevention level include water, sanitation, and hygiene interventions, breastfeeding, complementary feeding, vitamin A and zinc supplementation, and vaccines for diarrhea (rotavirus and cholera). Oral rehydration solution, zinc treatment, continued feeding, and antibiotic treatment for certain strains of diarrhea (cholera, Shigella, and cryptosporidiosis) are effective strategies for treatment of diarrhea. The recent Lancet series using the 'Lives Saved' tool suggested that if these identified interventions were scaled up to a global coverage to at least 80%, and immunizations to at least 90%; almost all deaths due to diarrhea could be averted. SUMMARY: The current childhood mortality burden highlights the need of a focused global diarrhea action plan. The findings suggest that with proper packaging of interventions and delivery platforms, the burden of childhood diarrhea can be reduced to a greater extent. All that is required is greater attention and steps toward right direction.

Airway mucus obstruction triggers macrophage activation and matrix metalloproteinase 12-dependent emphysema.

Whereas cigarette smoking remains the main risk factor for emphysema, recent studies in ß-epithelial Na(+) channel-transgenic (ßENaC-Tg) mice demonstrated that airway surface dehydration, a key pathophysiological mechanism in cystic fibrosis (CF), caused emphysema in the absence of cigarette smoke exposure. However, the underlying mechanisms remain unknown. The aim of this study was to elucidate mechanisms of emphysema formation triggered by airway surface dehydration. We therefore used expression profiling, genetic and pharmacological inhibition, Foerster resonance energy transfer (FRET)-based activity assays, and genetic association studies to identify and validate emphysema candidate genes in ßENaC-Tg mice and patients with CF. We identified matrix metalloproteinase 12 (Mmp12) as a highly up-regulated gene in lungs from ßENaC-Tg mice, and demonstrate that elevated Mmp12 expression was associated with progressive emphysema formation, which was reduced by genetic deletion and pharmacological inhibition of MMP12 in vivo. By using FRET reporters, we show that MMP12 activity was elevated on the surface of airway macrophages in bronchoalveolar lavage from ßENaC-Tg mice and patients with CF. Furthermore, we demonstrate that a functional polymorphism in MMP12 (rs2276109) was associated with severity of lung disease in CF. Our results suggest that MMP12 released by macrophages activated on dehydrated airway surfaces may play an important role in emphysema formation in the absence of cigarette smoke exposure, and may serve as a therapeutic target in CF and potentially other chronic lung diseases associated with airway mucus dehydration and obstruction.

The effects of sports drink osmolality on fluid intake and immunoendocrine responses to cycling in hot conditions.

We investigated the effects of two carbohydrate-based sports drinks on fluid intake and immunoendocrine responses to cycling. Six well-trained male cyclists completed trials on three separate days that involved cycling at 60% VO(2peak) for 90 min in hot conditions (28.1 ± 1.5ºC and 52.6 ± 3.1% relative humidity). During each trial, the subjects consumed ad libitum (1) an isotonic sports drink (osmolality 317 mOsm/kg), (2) a hypotonic sports drink (osmolality 193 mOsm/kg) or (3) plain water. The cyclists consumed significantly (p<0.05) more of the isotonic drink (1.23 ± 0.35 L) and hypotonic drink (1.44 ± 0.55 L) compared with water (0.73 ± 0.26 L). Compared with water (-0.96 ± 0.26 kg), body mass decreased significantly less after consuming the hypotonic drink (-0.50 ± 0.38 kg) but not the isotonic drink (-0.51 ± 0.41 kg). Blood glucose concentration was significantly higher at the end of the isotonic and hypotonic drink trials compared with the water trial. Neutrophil count and the plasma concentrations of catecholamines, interleukin 6 (IL-6), myeloperoxidase, calprotectin and myoglobin increased significantly during all three trials. IL-6 and calprotectin were significantly lower following the hypotonic drink trial compared with the water trial. In conclusion, hypotonic sports drinks are appealing for athletes to drink during exercise, and may help to offset fluid losses and attenuate some inflammatory responses to exercise.

Effects of dehydration on immune functions after a judo practice session.

We investigated the effects of dehydration after a judo practice session on player muscle and immune functions. Subjects included 25 female university judoists. Investigations were performed before and after 2.5 h of regular judo practice. Body composition, serum enzymes (myogenic enzymes, immunoglobulins and complements), neutrophils counts, reactive oxygen species (ROS) production capability, and phagocytic activity (PA) were measured. Subjects were divided into two groups according to level of dehydration after practice (mild dehydration and severe dehydration groups) and results were compared. Creatine kinase was found to increase significantly after practice. In addition, neutrophil count also increased significantly after practice in both groups. The changing ratios of IgA, IgG and C3 observed in the mild dehydration group were significantly higher than those in the severe dehydration group. In the severe dehydration group, post-practice PA/neutrophil had decreased significantly. Significant positive correlations were found between severity of dehydration and changing ratios of IgA, IgG, IgM, C3, C4 and ROS production capabilities, whereas no significant association was seen with PA and/or serum SOD activity. These results suggest that dehydration resulted in immunosuppression, including decreased neutrophil function.

Dehydration decreases saliva antimicrobial proteins important for mucosal immunity.

The aim of the study was to investigate the effect of exercise-induced dehydration and subsequent overnight fluid restriction on saliva antimicrobial proteins important for host defence (secretory IgA (SIgA), α-amylase, and lysozyme). On two randomized occasions, 13 participants exercised in the heat, either without fluid intake to evoke progressive body mass losses (BML) of 1%, 2%, and 3% with subsequent overnight fluid restriction until 0800 h in the following morning (DEH) or with fluids to offset losses (CON). Participants in the DEH trial rehydrated from 0800 h until 1100 h on day 2. BML, plasma osmolality (Posm), and urine specific gravity (USG) were assessed as hydration indices. Unstimulated saliva samples were assessed for flow rate (SFR), SIgA, α-amylase, and lysozyme concentrations. Posm and USG increased during dehydration and remained elevated after overnight fluid restriction (BML = 3.5% ± 0.3%, Posm = 297 ± 6 mosmol·kg⁻¹, and USG = 1.026 ± 0.002; P < 0.001). Dehydration decreased SFR (67% at 3% BML, 70% at 0800 h; P < 0.01) and increased SIgA concentration, with no effect on SIgA secretion rate. SFR and SIgA responses remained unchanged in the CON trial. Dehydration did not affect α-amylase or lysozyme concentration but decreased secretion rates of α-amylase (44% at 3% BML, 78% at 0800 h; P < 0.01) and lysozyme (46% at 3% BML, 61% at 0800 h; P < 0.01), which were lower than in CON at these time points (P < 0.05). Rehydration returned all saliva variables to baseline. In conclusion, modest dehydration (~3% BML) decreased SFR, α-amylase, and lysozyme secretion rates. Whether the observed magnitude of decrease in saliva AMPs during dehydration compromises host defence remains to be shown.

[Morphological changes in lymphoid nodules of small intestine in dehydration].

Morphological, cytological, morphometric changes were studied in single lymphoid nodules and in grouped lymphoid nodules (Peyers patches) of small intestine in albino rats after the dehydration lasting 3, 6, and 10 days and correction by administration of sodium chloride isotonic solution. In was found that the dehydration resulted in the decrease of lymphoid nodule dimensions, changes in the cellular proportions, enlargement of reticular fiber loops in the nodule stroma. On days 6 and 10 of dehydration, the percentages of macrophages, lymphocytes, cells showing the mitotic figures, mast cells and plasma cells were significantly decreased by factor of 1,4-4, indicating a depression of immune reactions.

Detection of a novel pattern of connexin 43 immunoreactivity responsive to dehydration in rat hypothalamic magnocellular nuclei.

Immunocytochemical expression of Connexin 43 (Cx 43) in the rat Supraoptic Nucleus was analyzed following dehydration, using sequence-specific anti-Cx 43 antibodies (designated 13-8300, 71-0700, and sc-9059) that exhibit differential recognition of Cx 43. Punctate and longitudinally arranged immunostaining patterns of Cx 43 labeling, as evidenced by antibody sc-9059, was detected overlaying the nucleus of magnocellular neuroendocrine cells. This novel form of longitudinally arranged Cx 43 immunoreactivity was modified by dehydration and halothane exposure, but not lactation.

Expression of mucin-type glycoprotein K88 receptors strongly correlates with piglet susceptibility to K88(+) enterotoxigenic Escherichia coli, but adhesion of this bacterium to brush borders does not.

Three antigenic variants of the K88 fimbrial adhesin exist in nature, K88ab, K88ac, and K88ad. Enterotoxigenic Escherichia coli (ETEC) strains that produce these fimbriae cause life-threatening diarrhea in some but not all young pigs. The susceptibility of pigs to these organisms has been correlated with the adherence of bacteria to isolated enterocyte brush borders. Whether that correlation holds for multiple K88 variants and over a broad genetic base of pigs is unknown and was the impetus for this study. We also desired to examine the correlation of the expression of a porcine intestinal brush border mucin-type glycoprotein (IMTGP) which binds K88ab and K88ac with the susceptibility of piglets to K88(+) ETEC. Of 31 neonatal gnotobiotic pigs inoculated with K88ab+ or K88ac+ ETEC, 13 developed severe diarrhea, became dehydrated, and died or became moribund. Another pig became severely lethargic but not dehydrated. In vitro brush border adherence analysis was not possible for 10 of the severely ill pigs due to colonization by challenge strains. However, of the 17 pigs that did not become severely ill, 8 (47%) had brush borders that supported the adherence of K88ab+ and K88ac+ bacteria in vitro, suggesting a poor correlation between in vitro brush border adherence and piglet susceptibility to K88(+) ETEC. By contrast, the expression of IMTGP was highly correlated with susceptibility to K88(+) ETEC. Of the 12 pigs that produced IMTGP, 11 developed severe diarrhea. The other pig that produced IMTGP became lethargic but not severely diarrheic. Only 2 of 18 pigs that did not produce IMTGP became severely diarrheic. Colonizing bacteria were observed in histologic sections of intestines from all pigs that expressed IMTGP except for the one that did not develop severe diarrhea. However, colonizing bacteria were observed in histologic sections from only one pig that did not produce IMTGP. The bacterial concentration in the jejuna and ilea of pigs expressing IMTGP was significantly greater (P < 0.005) than that in pigs not expressing IMTGP. These observations suggest the IMTGP is a biologically relevant receptor for K88ab+ and K88ac+ E. coli or a correlate for expression for such a receptor.

Homotypic immune response to primary infection with rotavirus serotype G1.

Some aspects of rotavirus humoral immunity were assessed on the basis of distinguishing serotype-specific specificities (VP4/VP7) by using rotavirus reassortants, human and animal strains in neutralization assays in serum samples obtained during the acute phase, and 1, 6 and 12 months after primary natural infection. In this study, all the infecting virus strains were characterized as G type and some also as P type. Primary natural infection induces a significantly greater homotypic neutralization response than heterotypic response. In addition, there was no significant difference in the number of homotypic or heterotypic responses following reinfection. Transplacentally acquired homotypic antibodies were associated with protection against dehydration during rotavirus gastroenteritis.

CD4+/CD8+ T-lymphocyte ratio: effects of rehydration before exercise in dehydrated men.

Effects of fluid ingestion on CD4+/CD8+ T-lymphocyte cell ratios were measured in four dehydrated men (ages 30-46 yr) before and after 70 min of supine submaximal (71% VO2max) lower extremity cycle exercise. Just before exercise, Evans blue dye was injected for measurement of plasma volume. The subjects then drank one of six fluid formulations (12 ml.kg-1) in 3-4 min. All six mean posthydration (pre-exercise) CD4+/CD8+ ratios (Becton-Dickinson Fluorescence Activated Cell Sorter and FACScan Consort-30 software program [San Jose, CA]) were below the normal range of 1.2-1.5; mean (+/- SE) and range were 0.77 +/- 0.12 and 0.39-1.15, respectively. The post-exercise ratios increased: mean = 1.36 +/- 0.15 (P < 0.05) and range = 0.98-1.98. Regression of mean CD4+/CD8+ ratios on mean plasma osmolality resulted in pre- and post-exercise correlation coefficients of -0.76 (P < 0.10) and -0.92 (P < 0.01), respectively. The decreased pre-exercise ratios (after drinking) were probably not caused by the Evans blue dye but appeared to be associated more with the stress (osmotic) of dehydration. The increased post-exercise ratios to normal levels accompanied the rehydration and were not due to the varied electrolyte and osmotic concentrations of the ingested fluids or to the varied vascular volume shifts during exercise. Thus, the level of subject hydration and plasma osmolality may be factors involved in the mechanism of immune system modulation induced by exercise.

Insulin-like immunoreactivity (IRI) in the rat hypothalamo-neurohypophysial system: effect of dehydration and haemorrhage.

Hypothalamic IRI was not affected in haemorrhaged rats, but diminished considerably in the dehydrated ones. In the neurohypohysis, IRI was distinctly higher both in dehydrated and haemorrhaged rats, i.e., under disorders which stimulated vasopressin and/or oxytocin release. It is suggested that insulin-like substance(s) may be someway involved in regulation of vasopressin or oxytocin secretion.

[Immunologic correction with immunoglobulin of toxemia with exicosis in infants with acute intestinal infections]. / Immunokorrektsiia immunoglobulinom pri toksikoze s éksikozom u detei pervogo goda zhizni s ostrymi kishechnymi infektsiiami.

The clinical course of acute intestinal infections complicated by toxicosis and exicosis was studied in 150 infants undergoing multimodality therapy, including natural human immunoglobulin for intravenous injections. The use of the new complex in the treatment of intestinal toxicoses was accompanied by increasing host immunological reactivity within short periods and decreasing of the treatment duration by 5.0 +/- 1.3 days; there were no persisting and chronic forms of the diseases and fatal outcomes. It was concluded that the use of the immunoglobulin for intravenous injections in the multimodality therapy of intestinal toxicoses in infants made it possible to prevent death in complicated intestinal infections and at the same time to accelerate their recovery.

Immunoreactive substance P in the tubero-hypophyseal system of the rat: selective decrease in the neural lobe after dehydration and sodium loading.

In the tubero-hypophyseal system of the rat the approximate concentrations of immunoreactive substance P (I-SP), expressed as fmol/mg tissue, were 100 in the medial basal hypothalamus (MBH), 20 in the anterior lobe (AL), 20 in the neural lobe (NL) and 4 in the intermediate lobe of the hypophysis. These values were not altered by treatment with capsaicin on day 2 after birth. In rats in which the secretion of neurohormones from the NL was increased by dehydration followed by sodium loading there was a fall by 70% in the I-SP concentration of the NL; no change occurred in the AL or the MBH.