Biomedical subjects

R W Johnson

Publications and source records attributed to R W Johnson.

At least 73 records · Page 4Linked to original sources

PubMed1998

Pretreatment of young pigs with vitamin E attenuates the elevation in plasma interleukin-6 and cortisol caused by a challenge dose of lipopolysaccharide.

The effect of a short-term, high-dose intramuscular injection of d-alpha-tocopherol was studied in pigs given a challenge dose of lipopolysaccharide (LPS). Twenty-four pigs surgically fitted with jugular catheters were used in a 2 x 2 factorial design. Pigs received either 0 or 600 mg d-alpha-tocopherol by intramuscular injection for 3 d before receiving an intraperitoneal injection of saline containing either 0 or 5 microgram/kg body weight Escherichia coli LPS. Blood was collected from indwelling jugular catheters at 0, 1, 2, 4, 6, 8, 12 and 24 h after injection of LPS. Plasma alpha-tocopherol levels were 13-fold greater (P < 0.01) at time 0 in pigs pretreated with 600 mg d-alpha-tocopherol (9.9 +/- 1.3 mg/L) than in those not treated with d-alpha-tocopherol (0.74 +/- 0.09 mg/L). Injection of LPS increased (P < 0.05) plasma levels of interleukin-6 (IL-6) and cortisol at 2-h postinjection, regardless of vitamin E treatment. However, pigs that received alpha-tocopherol before the LPS challenge had substantially lower (P < 0.05) peak levels of IL-6 and cortisol than pigs not receiving alpha-tocopherol. These results suggest that supplementation with a surfeit level of vitamin E reduces the response of pigs to endotoxin.

Animals↗

PubMed1998

Lipopolysaccharide-induced reductions in food intake do not decrease the efficiency of lysine and threonine utilization for protein accretion in chickens.

Exposure of animals to infectious agents induces immune responses that result in reductions in food consumption and weight gain. The effect of these changes on amino acid requirements and utilization remains unclear. Three assays were conducted with young chicks with Escherichia coli lipopolysaccharide (LPS) used to stimulate the immune system. An initial study was conducted to evaluate the effects of LPS on animal performance. In a daily or alternate day injection regimen for 9 d, chicks were given intraperitoneal injections of sterile saline containing 0, 100 or 400 microgram LPS. Administration of 100 or 400 microgram LPS daily, or every other day, decreased both weight gain and food consumption. In two subsequent growth assays, chicks were fed graded levels of lysine or threonine and injected with either 0 or 400 microgram LPS every other day to evaluate the effect of LPS administration on the efficiency of amino acid utilization. At the three lowest amino acid doses, whole-body protein accretion was a linear function of supplemental lysine or threonine intake, and slopes of the accretion curves were not altered by LPS administration. The dietary lysine concentration required to maximize protein accretion was unaffected by LPS, but the absolute lysine intake required to maximize chick performance was lower in LPS-injected chicks than in saline-injected chicks. These results show that LPS administration reduces weight gain, food intake, efficiency of food utilization and the absolute quantity of lysine required to maximize these criteria. However, LPS administration does not affect the efficiency of amino acid utilization, nor does it affect the concentration of dietary lysine required to maximize performance.

Animals↗

PubMed1998

Pre-emptive kidney transplantation: the attractive alternative.

BACKGROUND: Dialysis can be life-saving for patients with end-stage renal failure. However, not only is it associated with significant morbidity and a greater mortality than transplantation, but it is also expensive. Therefore renal transplantation is generally regarded as the treatment of choice for patients in whom this form of renal replacement therapy is appropriate. Transplantation usually takes place after a variable period of dialytic therapy, but pre-emptive kidney transplantation (PKT) has established itself as an attractive alternative. MATERIALS AND METHODS: 1463 consecutive first kidney transplants performed between January 1980 and December 1995 in a single centre were analysed. The 161 patients (11%) transplanted without prior dialysis were compared with the 1302 patients who had been dialysed prior to being transplanted. The pre-emptive group did not differ from the dialysis group in respect of donor age, donor and recipient gender, HLA mismatch, or cold ischaemic time, although there were more live donor transplants within the pre-emptive group. RESULTS: Delayed graft function occurred more frequently in the dialysis group (25% vs 16%) but more patients experienced an acute rejection episode in the pre-emptive group (67 vs 55%). The actuarial graft survival in the pre-emptive group at 1, 5, and 10 years (84, 76 and 67%) was significantly higher than the respective values in the dialysis group (83, 69, and 56%). Within the live donor recipient cohort the survival advantage for the pre-emptive group was even more striking. CONCLUSION: Pre-emptive kidney transplantation not only avoids the risks, cost, and inconvenience of dialysis, but is also associated with better graft survival than transplantation after a period of dialysis, particularly within the live donor cohort.

Adult↗

PubMed1998

Lipopolysaccharide-induced reductions in body weight gain and feed intake do not reduce the efficiency of arginine utilization for whole-body protein accretion in the chick.

The effects of repeated injections of 400 microg Escherichia coli lipopolysaccharide (LPS) on chick performance from 11 to 22 d posthatching were examined in chicks fed casein-based diets containing graded levels of arginine. Administration of LPS reduced (P < 0.05) weight gain, feed intake, and protein accretion, and there was a tendency (P=0.07) for LPS administration to be more growth-depressing at the higher than at the lower levels of supplemental arginine. Regression analysis of protein accretion for the first three doses of arginine indicated that protein accretion was a linear (P < 0.01) function of supplemental arginine intake for both saline-injected (r2=0.94) and LPS-injected (r2=0.93) chicks. Slopes of the best-fit regression lines for both treatment groups were equal, indicating that arginine utilization for protein accretion was not affected by LPS administration. The dietary arginine concentration required to maximize weight gain and feed efficiency was unaffected by LPS administration, with both saline- and LPS-injected chicks reaching plateaus in weight gain and feed efficiency at 0.90 and 0.98% digestible arginine, respectively.

Animals↗

PubMed1998

Interleukin-1beta-converting enzyme-deficient mice resist central but not systemic endotoxin-induced anorexia.

Interleukin-1beta (IL-1beta) mediates many of the behavioral responses to infection and inflammation, and IL-1beta-converting enzyme (ICE) processes intracellular IL-1beta, leading to its maturation and secretion. Here we demonstrate that intracerebroventricular injections of lipopolysaccharide (LPS) produced a greater reduction in both food intake and food-motivated behavior in wild-type compared with ICE-deficient (ICE -/-) mice. This defect occurred although ICE -/- mice were able to fully respond to intracerebroventricular injections of IL-1beta. In contrast, ICE -/- mice remained fully responsive to intraperitoneal injections of LPS. These results indicate that brain, but not peripheral, IL-1beta plays a critical role in the depression in food intake that occurs during inflammation.

Animals↗

PubMed1998

In vivo and in vitro evidence for the involvement of tumor necrosis factor-alpha in the induction of leptin by lipopolysaccharide.

To examine the role of tumor necrosis factor-alpha (TNF alpha) in mediating leptin secretion during an immunological challenge, we studied the effects of lipopolysaccharide (LPS) and TNF alpha on leptin secretion in endotoxin-sensitive C3H/HeOuJ (OuJ) mice, endotoxin-insensitive C3H/HeJ (HeJ) mice, and primary adipocytes cultured from both. Intraperitoneal injection of LPS increased plasma concentrations of TNF alpha and leptin in OuJ mice, but not in HeJ mice, suggesting a causal relationship between the induction of TNF alpha and leptin. Consistent with this idea, i.p. injection of recombinant murine TNF alpha increased plasma leptin in both OuJ and HeJ mice. To determine whether TNF alpha induces leptin secretion by acting directly on fat cells, primary adipocytes from OuJ and HeJ mice were cultured in the presence of TNF alpha or LPS. Whereas LPS was without effect on leptin secretion by adipocytes, TNF alpha induced a marked increase in the cell supernatant leptin concentration. These data demonstrate that TNF alpha plays a role in regulating the increase in leptin caused by LPS. Moreover, they show that TNF alpha can act directly on adipocytes to stimulate leptin secretion. Our results are consistent with the emerging view that leptin is a key hormone coupling immune system activity to energy balance.

Adipocytes↗

PubMed1998

Effects of feeder type, space allowance, and mixing on the growth performance and feed intake pattern of growing pigs.

The effect of crowding and mixing on growth performance and feed intake pattern were investigated in growing pigs in a 4-wk study. Feeding pattern was monitored using automated feed intake recording equipment (F.I.R.E.). A total of 256 Yorkshire x Hampshire and purebred Duroc pigs (initial weight 35.8+/-.86 kg) were allocated to one of the eight treatment combinations in a 2x2x2 factorial arrangement (feeder type [conventional feeder vs F.I.R.E. feeder], space allowance [.56 vs .25 m2/pig], and mixing strategy [mixed vs unmixed; mixing at start of wk 1 and 3]). Pigs were housed in groups of eight, balanced for genotype and sex (barrows and gilts), and had free access to a corn-soybean meal diet (17% crude protein, 3,296 kcal ME/kg). There was no difference in growth performance between feeder types. Crowding and mixing had no effect on daily feed intake but they depressed growth rate by 15.7 and 7.1%, respectively, and the effects of the two stressors were additive. Gain:feed ratio was reduced by crowding (10.0%) but not by mixing. Crowded pigs made fewer (11.2 vs 15.7; SEM = .51), and longer (12.5 vs 8.9 min; SEM .41) feeder visits and had higher feed intake per visit (196.2 vs 145.5 g; SEM = 5.94) than uncrowded animals. Mixing produced changes in feeding pattern in the 1st wk after mixing but not over the 4-wk period. This study showed that crowding and mixing depressed growth rates in an additive manner and altered feeding behavior.

Animal Feed↗

PubMed1998

Growth performance of pigs subjected to multiple concurrent environmental stressors.

The effects of many single stressors have been reported, but how pigs perform when subjected to more than one or two stressors at a time, as is common in commercial swine production, has not. To study this, 256 Yorkshire x Hampshire or purebred Duroc pigs (34.7+/-.5 kg) were subjected to one of the eight treatment combinations (2 x 2 x 2 factorial) of ambient temperature (constant thermoneutral [24 degrees C] or high cycling temperature [28 to 34 degrees C]), stocking density (.56 or .25 m2/pig), and social group (static group or regrouped at the start of wk 1 and 3) during a 4-wk experiment. The temperature regimens were imposed in two adjacent mechanically ventilated rooms, and each temperature was imposed in each room across two trials. Four barrows and four gilts were assigned to each of the eight pens in the two rooms, and they always had free access to water and a corn-soybean meal-based diet. Treatments were imposed after a 7-d acclimation period at 24 degrees C and .56 m2/pig. Weight gain and feed intake were measured weekly. The main effects of each of the stressors for 4-wk ADG and ADFI were significant (P < .05). The stress of high temperature, high stocking density, and regrouping depressed 4-wk ADG by 12, 16 and 10% and ADFI by 7, 6, and 5%, respectively. Of the possible 60 stressor interactions for ADG, ADFI, and gain:feed (G:F), there were no significant three-way interactions and only six two-way interactions, suggesting that the effects of the individual stressors were additive. Accordingly, the growth rate of pigs subjected to the single stressor of high cycling temperature, restricted space allowance, or regrouping was depressed 10, 16, and 11%, respectively, and ADG of pigs subjected to all three stressors simultaneously was depressed by 31%. Stressor additivity was further corroborated by examining the effect of stressor order, or the number of stressors imposed simultaneously. As the number of stressors increased from 0 to 3, ADG, ADFI, and G:F decreased linearly. These data suggest that multiple concurrent stressors affect growth performance of pigs in a predictable fashion (i.e., additively) and indicate that avoidance or removal of a given stressor is advantageous even when other uncontrollable stressors persist.

Animal Feed↗

PubMed1998

Economic and cultural influences on the decision to leave home in Peninsular Malaysia.

Although the departure of children from the parental home is an important life-cycle event, few studies have investigated nest-leaving in developing countries. Using retrospective data from the Second Malaysian Family Life Survey, we estimate hazard models of nest-leaving in Peninsular Malaysia. We find that the departure of children, especially sons, responds to economic incentives, including housing costs, family businesses, education, and economic growth, and that ethnic differences in nest-leaving are important. We also find that the median age of departure from home has declined sharply over the past 40 years, a period of rapid social and economic change in Malaysia.

Adolescent↗

PubMed1997

Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease.

This study was undertaken to determine if human recombinant growth hormone (hrGH, 6 mg/d for 2 wk) would stimulate muscle protein synthesis in AIDS wasting. Healthy controls were compared with patients who were HIV+, had AIDS without weight loss, and had AIDS with > 10% weight loss. Before hrGH, rates of skeletal muscle protein synthesis, measured with l-[2H5]phenylalanine, were the same in controls and in all stages of disease. Rates of myofibrillar protein degradation, however, assessed from urinary excretion of 3-methyl histidine, were higher in AIDS and AIDS wasting than in HIV+ or healthy individuals. The group with weight loss had significantly higher TNFalpha levels but not higher HIV viral loads. Muscle function, as determined by isokinetic knee extension and shoulder flexion, was significantly higher in controls than all infected individuals. After GH, rates of protein synthesis were stimulated 27% in controls, with a smaller increase (11%) in HIV+, and a significant depression (42%) in AIDS with weight loss, despite fourfold elevation in insulin-like growth factor-I in all groups. There was a significant correlation of hrGH-induced changes in muscle protein synthesis with severity of disease (P = 0.002). The results indicate increased basal muscle protein degradation and decreased responsiveness of muscle protein synthesis to GH in the later stages of disease.

Adult↗

PubMed1997

Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.

BACKGROUND: To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. METHODS: A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. RESULTS: At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. CONCLUSIONS: The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Adolescent↗

PubMed1997

Central interleukin-1 receptors as mediators of sickness.

These data establish that cytokines, such as IL-1, can act on specific receptors within the brain to induce many symptoms of sickness. A number of inflammatory stimuli in the periphery can activate both the transcription and translation of IL-1 within the central nervous system. It will now be important to determine if similar central IL-1 pathways are activated during SLE and whether these central inflammatory cytokines are involved in the neurologic complications that often accompany this disease.

Animals↗

PubMed1997

Anorexia, weight loss and increased plasma interleukin-6 caused by chronic intracerebroventricular infusion of interleukin-1beta in the rat.

Pro-inflammatory cytokines produced in the central nervous system (CNS) have been suggested to have a role in the anorexia and cachexia of disease. In the present study, the effects of chronic exposure of the CNS to interleukin-1beta (IL-1beta) on several indicators of cachexia were studied. Rats were prepared with an intracerebroventricular (i.c.v.) cannula and an osmotic minipump that delivered vehicle or 1.56 ng/h recombinant murine IL-1beta for 4 days. Food intake and body weight were determined daily during the 4-day infusion period and plasma IL-6 and corticosterone concentrations were determined from plasma collected postinfusion. Chronic i.c.v. infusion of IL-1beta resulted in a chronic reduction in food intake. Rats infused i.c.v. with IL-1beta ate less food each day compared to vehicle controls and, at the end of the 4-day infusion period, consumed an average of 17.2 g less. Intracerebroventricular infusion of IL-1beta also caused an immediate and substantial loss of body weight that was sustained throughout the infusion period. In addition, rats infused with IL-1beta had plasma levels of IL-6 double those of vehicle controls (401 pg/ml vs. 185 pg/ml). Plasma corticosterone concentrations were similar between treatments. These results suggest that chronic exposure of the CNS to cytokines such as IL-1beta may be sufficient to induce anorexia and cachexia.

Animals↗

PubMed1997

C3H/HeJ mice are refractory to lipopolysaccharide in the brain.

C3H/HeJ mice are refractory to lipolysaccharide (LPS) in the periphery, primarily because their macrophages do not respond to LPS and produce pro-inflammatory cytokines such as interleukin-1 (IL-1). To determine if they are also refractory to LPS in the brain, behavior of C3H/HeJ mice was compared to LPS-sensitive C3H/HeOuJ mice following intracerebroventricular (I.C.V.) injection of LPS. Whereas ICV injection of LPS (3-1000 ng/mouse) depressed social behavior, food motivation, object investigation and body weight in C3H/HeOuJ mice, C3H/HeJ mice were entirely refractory to LPS in the brain. To determine if the refractoriness of C3H/HeJ mice could result from an inability to synthesize IL-1, recombinant murine IL-1 was injected I.C.V. in both mouse strains. Central administration of IL-1 (1 or 2 ng/mouse) depressed social behavior and body weight similarly in both endotoxin-sensitive C3H/HeOuJ mice and endotoxin-resistant C3H/HeJ mice. That C3H/HeJ mice were refractory to the behavioral effects of central LPS, but not IL-1, suggests that microglia (and other cells in the brain) in C3H/HeJ mice have in common with peripheral macrophages, an inability to respond to LPS and produce cytokines. These data suggest a genetic basis for sickness behavior and demonstrate the utility of preventing central cytokine production in manipulating LPS-induced sickness behavior.

Animals↗

PubMed1997

Role of corticosterone in the behavioral effects of central interleukin-1 beta.

To investigate the role of the hypothalamic-pituitary-adrenal (HPA) axis in behavioral responses to infection, we studied the effects of corticosterone on depressed social behavior induced by peripheral and central interleukin-1 beta (IL-1 beta) in the rat. Intact and adrenalectomized (ADX) rats were injected i.p. with IL-1 beta (500 ng) and their motivation to investigate a juvenile conspecific was assessed. Whereas ADX rats showed a marked depression in social behavior following i.p. IL-1 beta, intact controls did not. To verify that corticosterone was responsible for inhibiting the effects of IL-1 beta, corticosterone pellets or placebos were implanted i.p. in ADX rats. Following i.p. injection of IL-1 beta, ADX rats with placebos experienced depressed social behavior. Corticosterone replacement, however, reversed this effect in ADX rats, confirming that corticosterone modulates the behavioral effects of peripheral IL-1 beta. To determine if corticosterone modulates sickness behavior directly in the CNS, intact and ADX rats were injected i.c.v. with IL-1 beta or lipopolysaccharide (LPS). Although centrally administered IL-1 beta depressed social behavior to a similar extent in intact and ADX rats, the depression was prolonged in ADX rats. However, social behavior of ADX rats injected i.c.v. with LPS was depressed more than in intact controls, and this effect was reversible by corticosterone replacement. These results are interpreted to indicate that corticosterone inhibits the behavioral effects of IL-1 beta in the periphery and, perhaps, in the CNS. That the behavioral effects of central LPS were inhibited by corticosterone suggests the HPA axis may modulate behavior by regulating cytokine synthesis in the CNS.

Animals↗

PubMed1997

Defect in interleukin-1beta secretion prevents sickness behavior in C3H/HeJ mice.

To examine the role of interleukin-1beta (IL-1beta) in mediating sickness, we studied the effects of lipopolysaccharide (LPS) and IL-1beta on social behavior in endotoxin-responsive C3H/HeOuJ (OuJ) mice and endotoxin-resistant C3H/HeJ (HeJ) mice. Whereas LPS (1, 10 and 100 microg) depressed social behavior and body weight compared to saline in OuJ mice, in HeJ mice it did not. To determine if the refractoriness of HeJ mice to the behavioral effects of LPS was related to secretion of IL-1beta, in a second study, HeJ and OuJ mice were injected IP with LPS (10 microg) and plasma concentration of IL-1beta was determined postinjection. At 4 h postinjection, the plasma concentration of IL-1beta was increased by LPS in OuJ mice, but not in HeJ mice. The increase in plasma IL-1beta in OuJ mice corresponded to the maximal depression in social behavior. To further verify that HeJ mice are refractory to the behavioral effects of LPS because they fail to respond and produce cytokines, the social behavior of HeJ and OuJ mice injected IP with recombinant murine IL-1beta (0, 50, 100, or 200 ng) was compared. As anticipated, exogenous IL-1beta depressed social behavior similarly in endotoxin-responsive OuJ mice and endotoxin-resistant HeJ mice. These data indicate that a genetic mutation in HeJ mice that prevents LPS-induced synthesis of cytokines also renders HeJ mice refractory to the behavioral effects of LPS.

Animals↗

PubMed1997

Induction of interleukin-1 beta-converting enzyme (ICE) in murine microglia by lipopolysaccharide.

Interleukin-1beta (IL-1beta) synthesized in the brain is thought to be involved in the behavioral response to LPS. In this study, we examined in microglia the ability of LPS to induce interleukin-1 beta-converting enzyme (ICE), the protease responsible for processing proIL-1beta to its mature biologically active form. The murine microglial cell line, N13, and primary microglia which had been previously isolated from brains of 2-d-old endotoxin-responsive C3H/HeOuJ mice and endotoxin-resistant C3H/HeJ mice, were cultured in the presence of various concentrations of LPS. Oligonucleotide primers for ICE and GAPDH were used in RT-PCR to determine the levels of ICE mRNA in microglia. ICE mRNA was constitutively expressed in N13 cells and primary microglia from both C3H/HeOuJ and C3H/HeJ mice. Upon exposure to LPS, ICE mRNA levels were markedly elevated in N13 cells and in microglia from C3H/HeOuJ mice, but not in microglia from endotoxin-resistant C3H/HeJ mice. Western immunoblotting was used to determine if the increase in ICE mRNA induced by LPS was accompanied by an increase in ICE protein. A modest increase in immunoreactivity for the p45 ICE precursor protein was evident in N13 cells and primary microglia from C3H/HeOuJ mice following exposure to LPS. Because corticosteroids inhibit the synthesis and secretion of IL-1beta, in a second experiment microglia were treated with LPS in the presence of dexamethasone (0, 10 and 100 microM). Dexamethasone inhibited the LPS-induced increase in ICE mRNA and protein in microglia from C3H/HeOuJ mice. These results indicate that LPS stimulates microglia to express ICE. That dexamethasone inhibited the expression of ICE, suggests that corticosteroids regulate the secretion of IL-1beta by microglial cells, in part, by regulating the expression of ICE.

Animals↗

PubMed1997

Hormones, lymphohemopoietic cytokines and the neuroimmune axis.

The classical distinction between hormones and cytokines has become increasingly obscure with the realization that homeostatic responses to infection involve coordinated changes in both the neuroendocrine and immune systems. The hypothesis that these systems communicate with one another is supported by the ever-accruing demonstrations of a shared molecular network of ligands and receptors. For instance, leukocytes express receptors for hormones and these receptors modulate diverse biological activities such as the growth, differentiation and effector functions. Leukocyte lineages also synthesize and secrete hormones, such as insulin-like growth factor-I (IGF-I), in response to both growth hormone (GH) and also to cytokines such as tumor necrosis factor-alpha (TNF-alpha). Since hormones share intracellular signaling substrates and biological activities with classical lymphohemopoietic cytokines, neuroendocrine and immune tissues share a common molecular language. The physiological significance of this shared molecular framework is that these homeostatic systems can intercommunicate. One important example of this interaction is the mechanism by which bacterial lipopolysaccharide, by eliciting a pro-inflammatory cytokine cascade from activated leukocytes, modulate pituitary GH secretion as well as other CNS-controlled behavioral and metabolic events. This article reviews the cellular and molecular basis for this communication system and proposes novel mechanisms by which neuroendocrine-immune interactions converge to modulate disease resistance, metabolism and growth.

Animals↗