Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation.

The dopaminergic system is involved in motivation, reward and the associated motor activities. Mesodiencephalic dopaminergic neurons in the ventral tegmental area (VTA) regulate motivation and reward, whereas those in the substantia nigra (SN) are essential for motor control. Defective VTA dopaminergic transmission has been implicated in schizophrenia, drug addiction and depression whereas dopaminergic neurons in the SN are lost in Parkinson's disease. Maternal immune activation (MIA) leading to in utero inflammation has been proposed to be a risk factor for these disorders, yet it is unclear how this stimulus can lead to the diverse disturbances in dopaminergic-driven behaviors that emerge at different stages of life in affected offspring. Here we report that gestational age is a critical determinant of the subsequent alterations in dopaminergic-driven behavior in rat offspring exposed to lipopolysaccharide (LPS)-induced MIA. Behavioral analysis revealed that MIA on gestational day 16 but not gestational day 12 resulted in biphasic impairments in motor behavior. Specifically, motor impairments were evident in early life, which were resolved by adolescence, but subsequently re-emerged in adulthood. In contrast, reward seeking behaviors were altered in offspring exposed MIA on gestational day 12. These changes were not due to a loss of dopaminergic neurons per se in the postnatal period, suggesting that they reflect functional changes in dopaminergic systems. This highlights that gestational age may be a key determinant of how MIA leads to distinct alterations in dopaminergic-driven behavior across the lifespan of affected offspring.

Shape Changes and Interaction Mechanism of Escherichia coli Cells Treated with Sericin and Use of a Sericin-Based Hydrogel for Wound Healing.

UNLABELLED: To verify the interaction mechanism between sericin and Escherichia coli, especially the morphological and structural changes in the bacterial cells, the antimicrobial activity of sericin against E. coli as a model for Gram-negative bacteria was investigated. The antibacterial activity of sericin on E. coli and the interaction mechanism were investigated in this study by analyzing the growth, integrity, and morphology of the bacterial cells following treatment with sericin. The changes in morphology and cellular compositions of bacterial cells treated with sericin were observed by an inverted fluorescence microscope, scanning electron microscopy, and transmission electron microscopy. Changes in electrical conductivity, total sugar concentration of the broth for the bacteria, and protein expression of the bacteria were determined to investigate the permeability of the cell membrane. A sericin-based hydrogel was prepared for an in vivo study of wound dressing. The results showed that the antibacterial activity of the hydrogel increased with the increase in the concentration of sericin from 10 g/liter to 40 g/liter. The introduction of sericin induces membrane blebbing of E. coli cells caused by antibiotic action on the cell membrane. The cytoplasm shrinkage phenomenon was accompanied by blurring of the membrane wall boundaries. When E. coli cells were treated with sericin, release of intracellular components quickly increased. The electrical conductivity assay indicated that the charged ions are reduced after exposure to sericin so that the integrity of the cell membrane is weakened and metabolism is blocked. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that sericin hinders the expression of bacterial protein. Sericin may damage the integrity of the bacterial cell membrane, thereby eventually inhibiting the growth and reproduction of E. coli Compared to sterile gauze, the sericin-based hydrogel promoted fibroblast cell proliferation and accelerated the formation of granulation tissues and neovessels. IMPORTANCE: The specific relationship and interaction mechanism between sericin and E. coli cells were investigated and elucidated. The results show that after 12 h of treatment, sericin molecules induce membrane blebbing of E. coli cells, and the bacteria show decreases in liquidity and permeability of biological membrane, resulting in alterations in the conductivity of the culture medium and the integrity of the outer membrane. The subsequent in vivo results demonstrate that the sericin-poly(N-isopropylacrylamide-N,N'-methylene-bis-acrylamide [NIPAm-MBA]) hydrogel accelerated wound healing compared to that with sterile gauze, which is a beneficial result for future applications in clinical medicine and the textile, food, and coating industries.

The deficiency of myelin in the mutant taiep rat induces a differential immune response related to protection from the human parasite Trichinella spiralis.

Taiep rat is a myelin mutant with a progressive motor syndrome characterized by tremor, ataxia, immobility episodes, epilepsy and paralysis of the hindlimbs. Taiep had an initial hypomyelination followed by a progressive demyelination associated with an increased expression of some interleukins and their receptors. The pathology correlated with an increase in nitric oxide activity and lipoperoxidation. In base of the above evidences taiep rat is an appropriate model to study neuroimmune interactions. The aim of this study was to analyze the immune responses in male taiep rats after acute infection with Trichinella spiralis. Our results show that there is an important decrease in the number of intestinal larvae in the taiep rat with respect to Sprague-Dawley control rats. We also found differences in the percentage of innate and adaptive immune cell profile in the mesenteric lymphatic nodes and the spleen that correlated with the demyelination process that took place on taiep subjects. Finally, a clear pro-inflammatory cytokine pattern was seen on infected taiep rats, that could be responsible of the decrement in the number of larvae number. These results sustain the theory that neuroimmune interaction is a fundamental process capable of modulating the immune response, particularly against the parasite Trichinella spiralis in an animal model of progressive demyelination due to tubulinopathy, that could be an important mechanism for the clinical course of autoimmune diseases associated with parasite infection.

An immunocompetent rat model of infection with Cryptosporidium hominis and Cryptosporidium parvum.

A major obstacle to developing vaccines against cryptosporidiosis, a serious diarrheal disease of children in developing countries, is the lack of rodent models essential to identify and screen protective immunogens. Rodent models commonly used for drug discovery are unsuitable for vaccine development because they either are purposefully immunodeficient or immunosuppressed. Here, we describe the development and optimization of an immunocompetent intratracheal (IT) rat model susceptible to infections with sporozoites of Cryptosporidium parvum and Cryptosporidium hominis - the primary causes of human cryptosporidiosis. A model suitable for screening of parasite immunogens is a prerequisite for immunogen screening and vaccine development.

Non-invasive neuromodulation using rTMS and the electromagnetic-perceptive gene (EPG) facilitates plasticity after nerve injury.

BACKGROUND: Twenty million Americans suffer from peripheral nerve injury. These patients often develop chronic pain and sensory dysfunctions. In the past decade, neuroimaging studies showed that these changes are associated with altered cortical excitation-inhibition balance and maladaptive plasticity. We tested if neuromodulation of the deprived sensory cortex could restore the cortical balance, and whether it would be effective in alleviating sensory complications. OBJECTIVE: We tested if non-invasive repetitive transcranial magnetic stimulation (rTMS) which induces neuronal excitability, and cell-specific magnetic activation via the Electromagnetic-perceptive gene (EPG) which is a novel gene that was identified and cloned from glass catfish and demonstrated to evoke neural responses when magnetically stimulated, can restore cortical excitability. METHODS: A rat model of forepaw denervation was used. rTMS was delivered every other day for 30 days, starting at the acute or at the chronic post-injury phase. A minimally-invasive neuromodulation via EPG was performed every day for 30 days starting at the chronic phase. A battery of behavioral tests was performed in the days and weeks following limb denervation in EPG-treated rats, and behavioral tests, fMRI and immunochemistry were performed in rTMS-treated rats. RESULTS: The results demonstrate that neuromodulation significantly improved long-term mobility, decreased anxiety and enhanced neuroplasticity. The results identify that both acute and delayed rTMS intervention facilitated rehabilitation. Moreover, the results implicate EPG as an effective cell-specific neuromodulation approach. CONCLUSION: Together, these results reinforce the growing amount of evidence from human and animal studies that are establishing neuromodulation as an effective strategy to promote plasticity and rehabilitation.

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.

Colony-Specific Differences in Endocrine and Immune Responses to an Inflammatory Challenge in Female Sprague Dawley Rats.

Sprague Dawley rats from different vendor colonies display divergent responses in a variety of experimental paradigms. An adjuvant-induced arthritis (AA) model of human rheumatoid arthritis was used to examine immune and endocrine responses to inflammatory challenge in Sprague Dawley rats from Charles River and Harlan colonies. Rats were injected with either complete Freund's adjuvant or physiological saline (control), weights, and paw volumes measured over 15 days, and blood and tissue were collected 16 days post-injection. Overall, Harlan rats developed more severe AA than Charles River rats. In addition, despite comparable corticosterone levels, corticosteroid binding globulin levels were lower in Harlan compared with Charles River rats in the absence of inflammation, suggesting that a lower corticosterone reservoir in Harlan rats may underlie their greater susceptibility to inflammation. With increasing AA severity, there was an increase in plasma corticosterone (total and free) and a decrease in corticosteroid binding globulin in both Charles River and Harlan rats. However, contrasting patterns of cytokine activation were observed in the hind paw, suggesting a reliance on different cytokine networks at different stages of inflammation, with Charles River rats exhibiting increased TNF-α, monocyte chemotactic protein-1 (MCP-1), keratinocyte chemoattractant/growth-regulated oncogene (KC/GRO), and IL-1ß in the absence of clinical signs of arthritis, whereas Harlan had increased TNF-α, monocyte chemotactic protein-1, and IL-6 with mild to moderate arthritis. These colony-specific differences in endocrine and immune responses to AA in Sprague Dawley rats must be considered when comparing data from different laboratories and could be exploited to provide insight into physiological changes and therapeutic outcomes in arthritis and other inflammatory disorders.

Altered c-fos expression in the parabrachial nucleus in a rodent model of CFA-induced peripheral inflammation.

Increases in the expression of immediate early genes have been shown to occur in the lumbar spinal cord dorsal horn after peripheral inflammation. Given that the pontine parabrachial nucleus has been implicated in nociceptive as well as antinociceptive processes and is reciprocally connected with the spinal cord dorsal horn, it seems likely that peripheral inflammation will cause alterations in immediate early gene expression in this nucleus. To test this hypothesis we examined cFos-like immunoreactivity in a rodent complete Freund's adjuvant-induced peripheral inflammatory model of persistent nociception. Unilateral hind paw injections of complete Freund's adjuvant produced inflammation, hyperalgesia of the affected limb, and alterations in open field behaviors. Immunocytochemical analysis demonstrated a bilateral increase in cFos-like immunoreactivity in the lateral and Kolliker-Fuse subdivisions of the parabrachial nucleus at 6 and 24 hours postinjection and an ipsilateral decrease below basal levels in the Kolliker-Fuse subdivision at 96 hours postinjection when compared to saline controls. Taken together, these results suggest that select parabrachial neurons are activated by noxious somatic inflammation. These active parabrachial neurons are likely to participate in ascending nociceptive and/or descending antinociceptive pathways.

Regulation of the gene encoding the monocyte chemoattractant protein 1 (MCP-1) in the mouse and rat brain in response to circulating LPS and proinflammatory cytokines.

Accumulating evidence supports the existence of an innate immune response in the brain during systemic inflammation that is associated with a robust induction of proinflammatory cytokines and chemokines by specific cells of the central nervous system. The present study investigated the genetic regulation and fine cellular distribution of the monocyte chemoattractant protein-1 (MCP-1) in the brain of mice and rats in response to systemic immune insults. MCP-1 belongs to a superfamily of chemokines that have a leading role in the early chemotaxic events during inflammation. In situ hybridization histochemistry failed to detect constitutive expression of the chemokine transcript in the cerebral tissue except for the area postrema (AP) that exhibited a low signal under basal conditions. This contrasts with the strong and transient induction of the mRNA encoding MCP-1 following a single systemic bolus of lipopolysaccharide (LPS), recombinant interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha). These stimuli rapidly triggered (30 to 90 minutes) MCP-1 transcription in all the circumventricular organs (CVOs), the choroid plexus (chp), the leptomeninges, and along the cerebral blood vessels. The time-related induction and intensity of the signal differed among the challenges, route of administration and species, but MCP-1-expressing cells were always found in vascular-associated structures and those devoid of blood-brain barrier. At later times, few isolated microglia across the brain parenchyma depicted positive signal for MCP-1 mRNA. A dual-labeling procedure also provided convincing anatomical evidence that endothelial cells of the microvasculature and a few myeloid cells of the CVOs and chp were positive for the transcript during endotoxemia. This gene is under a sophisticated transcriptional regulation, as the hybridization signal returned to undetectable levels 12 to 24 hours after all the treatments in both species. Of interest are the data that only ligands that triggered nuclear factor kappa B (NF-kappa B) signaling had the ability to increase MCP-1 gene expression, because high doses of IL-6 remained without effects. These data provide the anatomical evidence that MCP-1 is expressed within specific populations of cells in response to systemic inflammatory molecules that use NF-kappa B as intracellular signaling system. This chemokine may therefore play a critical role in the cerebral innate immune response and contribute to the early chemotaxic events during chronic cerebral inflammation.

MHC expression in nonlymphoid tissues of the developing embryo: strongest class I or class II expression in separate populations of potential antigen-presenting cells in the skin, lung, gut, and inter-organ connective tissue.

We define expression of major histocompatibility complex (MHC) antigens in the nonlymphoid tissues of the developing rat. Antibodies to class I heavy and light chains (b2-m), and to class II MHC proteins were used. Strongest MHC expression was by individual cells in the skin, lung, gut, and inter-organ connective tissue. The class I+ and class II+ cells were distinct populations, differing in morphology, distribution, and expression of macrophage-associated antigens. A nonimmunologic role for MHC proteins in development has been proposed. Yet the distributions and antigenic profiles lead us to emphasize immunologic functions that may be served by the early presence of MHC+ cells outside the forming lymphoid organs. Potential contributions to establishment of extrathymic or maternal/fetal tolerance are discussed. Localization of strongest MHC expression to individual connective tissue cells of the developing organs, rather than parenchymal cells, is of clinical relevance to transplantation of fetal tissue.

Fibrin degradation products in growth stimulatory extracts of pathological lesions.

We have previously shown that similar patterns of fibrin degradation products (FbDP) by gel electrophoresis and immunoblotting are present in extracts of human atherosclerotic plaques, human and experimental wounds and breast cancers. Such extracts were also shown to stimulate cell proliferation including angiogenesis in the chick chorioallantoic membrane, now shown also for breast cancers. Removal of FbDP from plaque extracts by an anti-fibrinogen affinity column, or by an anti-fragment E column, reduced activity. Human FbDP prepared in vitro were active, but not FgDP. Fibrin fragment E was active, and we also showed that admixture of FbDP with a polyclonal rabbit anti-fibrin E but not anti-fibrin D neutralized activity. However attempts to raise comparable monoclonal blocking antibodies were hindered by species similarities. The response of the Balb/c mouse was predominantly directed at minor D contaminants, in contrast to the Sprague-Dawley rat which responded to fibrin fragment E in our antigen preparation.

Host response to mycobacterial infection in the alcoholic rat: male and female dimorphism.

Increased susceptibility to tuberculosis occurs in the alcoholic. One explanation for the altered susceptibility is a change in T-lymphocyte modulation. To evaluate this, 24 male and 24 female Sprague-Dawley rats were treated with either a Lieber-type liquid ethanol diet (LED) or an isocaloric control (LCD). After 2 weeks, half the subjects were infected with BCG (10(8) colony-forming units) and sacrificed after 42 days. Splenic helper (CD4) and suppressor/cytoxic (CD8) cells were quantitated by flow cytometry. By three-way analysis of variance, splenic cellularity was significantly increased by infection (p < 0.0001) but suppressed by LED (p = 0.0002). There was a marginal sexual difference (p = 0.065) with females exhibiting a 35% lower response while on alcohol. Examining lymphocyte subsets, the most significant changes were observed after infection (BCG) and alcohol treatment (LED). CD4 levels were diminished by LED (p = 0.0002) but markedly increased by infection (p < 0.0001), producing a highly significant interaction that affected both absolute number (p < 0.0001) and relative percent present (p = 0.0078). CD8 was influenced only by infection (p < 0.0001). This resulted in a infection-related increase in the CD4/CD8 ratio which was lower with LED (p = 0.0032). Splenic T-lymphocytes, predominately CD4, are involved in the host response to BCG hepatitis and are adversely influenced by LED, which may contribute to increased susceptibility.

Effects of purified soybean agglutinin on growth and immune function in rats.

The objective of this study was to investigate the effect of purified soybean agglutinin on growth and immune function in rats. Thirty male Sprague-Dawley rats (77.8 +/- 2.6 g) were individually fed casein-cornstarch based diets containing 0, 0.05, 0.10, 0.15 or 0.20% soybean agglutinin (w/w) during a 20-day experiment. Growth declined linearly with increasing the concentration of soybean agglutinin (p < 0.05). The proliferation of lymphocytes in spleen, lymph nodes and blood decreased with an increase in dietary soybean agglutinin (p < 0.05). The concentrations of interleukin-2, interferon-gamma and tumor necrosis factor-alpha in plasma, spleen, and mesenteric lymph nodes as well as plasma concentrations of IgA, IgG and IgM also declined with increasing dose of soybean agglutinin (p < 0.05). The results show that dietary soybean agglutinin has negative effects on growth as well as both cell-mediated and humoral immune function of rats and appears to function in a dose-dependent manner.

Enhancement of antigen-specific humoral and cell-mediated immunity by electric footshock stress in rats.

The effect of footshock stress on the induction phase of sensitization to keyhole limpet hemocyanin (KLH) introduced intraperitoneally was studied in adult male Sprague-Dawley rats. Rats were shocked at Days -1, 0, 1, and 3 relative to sensitization with 50 micrograms KLH and 14 days later were intradermally injected with 25 micrograms KLH or were noninjected. Anti-KLH IgG levels were measured in serum by ELISA and were enhanced in stressed versus control rats shocked on Days 0 or 1; splenocyte proliferation to KLH in vitro was also found to be enhanced in shocked rats compared to that in nonshocked rats. Skin at the challenge sites was removed and histologically examined for infiltrate density. There was an increased infiltrate in animals shocked on Days 0 or 1 in comparison to nonshocked controls. The increased humoral and cell-mediated anti-KLH immunity in stressed rats is evidence for enhanced immune function by exposure to footshock proximal to the induction phase of the immune response. The possibility of a generalized increase in immune function in stressed rats is doubtful since splenocyte proliferation to the T-cell mitogens concanavalin A (Con A) and phytohemagglutinin and the B-cell mitogen lipopolysaccharide showed no alteration between control and stressed rats at the time of sacrifice.

Dietary effect of guar gum and its partially hydrolyzed product on the lipid metabolism and immune function of Sprague-Dawley rats.

The dietary effect of the water-soluble dietary fibers (WSDF), guar gum, partially hydrolyzed guar gum (PHGG), glucomannan, highly methoxylated (HM) pectin, on the serum lipid level and immunoglobulin (Ig) production of Sprague-Dawley rats was compared with that of water-insoluble cellulose. Although serum total cholesterol and triglyceride levels were significantly lower in the rats fed with WSDF than in those fed with cellulose, a decrease in the level of phospholipids was only observed in the rats that had been fed on guar gum or glucomannan. In addition, all WSDF feeding enhanced IgA productivity in the spleen and mesenteric lymph node lymphocytes, although the increase in serum IgA level was only observed in the rats fed on WSDF, and not on PHGG. When mesenteric lymph node lymphocytes were cultured in the presence of various concentrations of guar gum or glucomannan, no significant increase in Ig production was apparent. These data suggest that WSDF indirectly enhanced the Ig production of lymphocytes, and that serum lipid reduction and IgA production-enhancing activities of WSDF were dependent on their molecular sizes.

Quantitative phenotypic and functional analyses of islet immune cells before and after diabetes onset in the BB rat.

Inflammatory cells invading islets are thought to be mediators of islet destruction in spontaneous autoimmune diabetes mellitus. Thus methods were developed to isolate and characterize in situ islet inflammatory cells from 75-95-day-old prediabetic and diabetic BB rats. Islet inflammatory cells were structurally examined using single- and double-colour flow cytometry. Functional studies consisted of cytolytic assays using normal rat islet target cells and in situ islet or spleen effector cells. Structural data reveal natural killer cells to be the major cell population (70%) of total immune cells present in inflamed islets during prediabetes. At diabetes onset, the natural killer cell population remained at a high level (47%), but an increasing population of T cells (40%) was noted also. Analyses of T-cell subsets before and after diabetes onset revealed CD4+ T cells as predominant (50-55% of total T cells) with double-negative (CD4-CD8-) T cells (25-30%) and CD8+ T cells (15-20%) also present in significant quantities. Activated T cells accounted only for a minority of T cells (< 3%). Functional studies indicate that in situ islet-derived cytolytic effector cells are more potent killers (ten-fold) of normal islet target cells than are splenic effector cells. These data suggest that in situ islet inflammatory cells (a) can be quantitatively studied both structurally and functionally; (b) express structural phenotypes differing substantially from splenic mononuclear cell populations; (c) are considerably more cytolytic than splenic effectors; and (d) should prove informative in determining the most significant autoimmune functional events prior to and during islet beta-cell destruction.

Cloning of the complete rat immunoglobulin delta gene: evolutionary implications.

The recent discovery of a Cdelta encoding gene in artiodactyls has raised questions regarding the evolution of the gene. In the present study, we have analysed the complete rat Cdelta gene both at the cDNA and genomic levels, showing that the rat Cdelta gene is structurally similar to the corresponding mouse gene. Analysis of the rat immunoglobulin D heavy chain cDNA tail sequences, revealed two transcripts for the secreted form with varying sizes of their 3' untranslated region (UTR), resulting from usage of two different poly(A) addition signals. Furthermore, a membrane-bound form encoding transcript, possessing a long 3' UTR, was also observed. Phylogenetic analysis supports that the Cdelta gene appeared early in the evolution of vertebrates, and it was probably duplicated from the C micro gene more than 400 million years ago.

Measurement of airborne rat urinary allergen in an epidemiological study.

The suitability of radioallergosorbent test (RAST) inhibition to quantify occupational exposure to rat urinary aeroallergen (RUA) has been assessed. When using a constant pool of rat allergic sera, the reproducibility of the assay over 1 year was comparable to that reported for other immunoassays; at 50% RAST inhibition the inter-assay coefficient of variation (CV) was 7.0% and the intra-assay CV was 3.0%. The assay was highly specific for rat urine; mouse urine was 1100-fold less potent at inhibiting the rat urine RAST system. Significant inter-assay variation in the 'high' control was not due to batch variation and was relatively small when compared with the variation in RUA concentrations in the occupational environment. Measurement of workplace RUA exposure demonstrated that those directly involved in the care of rats experienced the highest RUA exposure of the nine occupational groups studied (animal technicians GM = 23.10 micrograms/m3), dead animals (e.g. post mortem GM = 1.60 micrograms/m3, scientists GM = 0.67 microgram/m3) and rat tissue (e.g. slide production GM = 0.04 microgram/m3). In view of the complexity of rat allergens, RAST inhibition is an appropriate method for the quantification of occupational exposure to rats.

Sprague-Dawley rats obtained from different vendors exhibit distinct adrenocorticotropin responses to inflammatory stimuli.

The purpose of this work was to compare the plasma adrenocorticotropin (ACTH), corticosterone and interleukin-6 (IL-6) responses that rats of the outbred Sprague-Dawley strain obtained from two different vendors: Charles River (CR) and Harlan (HSD). Basal plasma ACTH and IL-6 concentrations were similar in rats from either vendor (HSD or CR), while CR animals exhibited slightly elevated corticosterone levels in late afternoon. Inflammatory stimuli such as lipopolysaccharide (LPS) (1 microgram/kg, i.v.) or turpentine (50 microliter/100 g, i.m.) which induce the production of endogenous cytokines, produced a significantly larger ACTH response in CR, compared to HSD rats, while the overall corticosterone responses were comparable in both rat groups. This could probably not be accounted for by a greater ACTH responsiveness in CR rats per se because CR and HSD rats showed similar peak ACTH responses to electrofootshock. Furthermore, in contrast to when the stimulus was one that induced endogenous cytokine production, the administration of exogenous interleukin-1beta (IL-1beta, 200 ng/kg, i.v.) produced a 2-fold greater rise in plasma ACTH concentrations in HSD rats compared to CR rats. The plasma IL-6 responses to the inflammatory stimuli showed a similar pattern to ACTH, with LPS and turpentine tending to pruduce greater IL-6 responses in CR rats, though these differences were not statistically significant. In contrast HSD rats had a significantly greater IL-6 response to IL-1beta than did CR rats. Collectively, these results show that Sprague-Dawley rats obtained from different commercial sources can differ in immune-neuroendocrine responses to inflammatory stimuli.