Evidence of acute phase reaction in asymptomatic dogs naturally infected with Babesia canis.

Asymptomatic outdoor dogs can be carriers of Babesia canis, but data describing the development of an acute phase response (APR) are not available. We hypothesised that these dogs have a moderate APR that could be detected by hematological and biochemical changes. Two groups of Babesia-exposed dogs were represented by nine B. canis PCR-positive and twenty B. canis PCR-negative, seroreactive dogs. The control group consisted of ten Babesia-naïve dogs. Serum amyloid A (SAA), paraoxonase-1 (PON-1), complete blood count, and biochemistry parameters were analysed by standard methodologies. Protein and lipoprotein fractions were separated using agarose gel electrophoresis (GE), and the dominant diameters of lipoproteins were assessed on gradient GE. Results were evaluated using non-parametric tests and the Receiver Operating Characteristic curve. SAA (median 39.0 µg/mL, range 2.2-48.8 µg/mL), total protein (median 74.7 g/L, range 57.1-98.3 g/L) and the dominant diameter of α-lipoproteins (median 13.31 nm, range 12.09-14.17 nm) in B. canis PCR-positive dogs were higher relative to dogs in the control group or dogs that were PCR-negative but seroreactive (p < 0.001 for both groups). Mild to moderate anemia (4/29), thrombocytopenia (7/29), and leukocyte counts that were close to the upper limit of the reference range were encountered in both Babesia-exposed groups. When compared to controls, Babesia-exposed dogs displayed decreased a PON-1 activity and protein GE pattern consistent with low-grade chronic inflammation (p < 0.001 for both groups). Dogs with detectable amounts of B. canis DNA in blood contain increased levels of SAA and total protein along with α-lipoproteins that display an increased diameter relative to those dogs with positive Babesia serology but undetectable levels of B. canis DNA in blood.

Association of acute Babesia canis infection and serum lipid, lipoprotein, and apoprotein concentrations in dogs.

BACKGROUND: Babesia canis infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis. HYPOTHESIS: Dogs with B. canis-induced APR develop dyslipidemia with altered lipoprotein concentration and morphology. ANIMALS: Twenty-nine client-owned dogs with acute B. canis infection and 10 clinically healthy control dogs. METHODS: Observational cross-sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA-1 (radioimmunoassay) and SAA was determined. RESULTS: Dogs with B. canis infection had a marked APR (median SAA, 168.3 µg/mL; range, 98.1-716.2 µg/mL) compared with controls (3.2 µg/mL, 2.0-4.2 µg/mL) (P < .001). Dogs with B. canis infection had significantly lower median cholesterol (4.79 mmol/L, 1.89-7.64 mmol/L versus 6.15 mmol/L, 4.2-7.4 mmol/L) (P = .02), phospholipid (4.64 mmol/L, 2.6-6.6 mmol/L versus 5.72 mmol/L, 4.68-7.0 mmol/L) (P = .02), and α-lipoproteins (77.5%, 27.7%-93.5% versus 89.2%, 75.1%-93.5%) (P = .04), and higher ApoA-1 (1.36 U, 0.8-2.56 U versus 0.95 U, 0.73-1.54 U) concentrations (P = .02). Serum amyloid A correlated with high-density lipoproteins (HDLs) diameter (rho = .43; P = .03) and ApoA-1 (rho = .63, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Major changes associated with B. canis-induced APR in dogs are related to concentration, composition, and morphology of HDL particles pointing to an altered reverse cholesterol transport. Parallel ApoA-1 and SAA concentration increase is a unique still unexplained pathophysiological finding.

Acute phase response in organic lambs associated with colostrum serum amyloid A, weight gain, and Cryptosporidium and Giardia infections.

In neonatal period, lamb's immune system goes through rapid adaptation to the extra-uterine environment. Success of this process can influence the animal's future performance and, thus, the quantitative assessment of it would greatly benefit sheep producers. The current study was conducted to investigate the acute phase response (APR) (measured through serum amyloid A (SAA), haptoglobin (Hp) and albumin (ALB)) in relation to later life growth (measured at 122 days of age), and naturally occurring Cryptosporidium and Giardia infections in neonatal lambs grown in organic farm. Serum (n = 692) and faecal (n = 141) samples were collected from 269 lambs in their first 3 weeks of life. The ewes' colostrum (n = 181) SAA concentrations were positively associated with the lambs' serum SAA and Hp concentrations at 2 to 4 days of age. Hp and ALB concentrations at the second week of age were positively associated with the growth rate at 122 days of age. Lamb serum globulin (GLOB) concentrations and Cryptosporidium-positive faecal samples were negatively associated at the second and third weeks of life. These findings suggest the importance of interactions between the immune system and environmental factors at the second week of the lambs' lives and its association with future performance.

Acute-phase response in Babesia canis and Dirofilaria immitis co-infections in dogs.

Babesia canis and Dirofilaria immitis are emerging and geographically overlapping vector-borne pathogens in dogs. Infection with B. canis leads to acute-phase response (APR) that can be mild to severe and results in either non-complicated or complicated forms of the disease. The aim of this study was to determine whether acute B. canis infection is more severe in dogs with underlying asymptomatic D. immitis infection. Dogs of both sexes, different ages and breeds, with naturally occurring mono-infections with B. canis (n=13) and D. immitis (n=18) and co-infected dogs (n=7) were enrolled as well as healthy controls (n=15). Routine haematology and biochemistry, agarose gel electrophoresis (agEF) protein fraction separation and enzyme-linked immunosorbent assay (ELISA) for serum amyloid A (SAA) were performed. Based on clinical and laboratory findings, sepsis was diagnosed in the majority of dogs with acute B. canis infection with or without underlying asymptomatic D. immitis infection. Overall, haematology, biochemistry and agEF pattern changes were induced and dictated by acute B. canis infection whether or not the dogs had an asymptomatic D. immitis infection. D. immitis infection slightly influenced the level of anaemia, slightly aggravated the level of dehydration and increased the concentration of γ-globulins in acute-phase B. canis infection. D. immitis infection prevented B. canis-induced leukopenia. SAA equally increased in dogs with acute B. canis infection with or without underlying D. immitis infection. The level of SAA was not changed in dogs with asymptomatic D. immitis when compared to the controls. In conclusion, asymptomatic D. immitis infection does not influence overall APR after acute B. canis infection.

Parasite distribution and associated immune response during the acute phase of Toxoplasma gondii infection in sheep.

BACKGROUND: In many countries, Toxoplasma gondii (T. gondii) is a major cause of reproductive disorders and abortions in the sheep industry, and therefore responsible for important financial and economic losses. In addition, undercooked infected lamb is an important risk factor for human toxoplasmosis. In the present study, the initial phase of the infection was investigated: the parasite's entry site, the subsequent distribution of the parasite and the host-immune response. RESULTS: Parasite DNA was already detected in the cranial small intestinal mucosa the first days after oral infection with T. gondii tissue cysts. Simultaneously, high IFN-gamma and IL-12 responses were induced mainly in the mesenteric lymph nodes. The emergence of IgG1 (at 8dpi), and IgG2 (at 11 dpi) was accompanied by a decrease or even disappearance of the IFN-gamma and IL-12 response in the Peyers' patches (PP), PBMC's and popliteal LN's. Meanwhile the parasite DNA could be recovered from most mucosal and systemic tissues to become undetectable in the small intestine, popliteal LN, PBMC and spleen 3 weeks pi. CONCLUSIONS: Our results indicate that parasites enter the cranial small intestine the first days after infection and that after an increase the first two weeks after infection, the parasite DNA levels in the intestine drop below the detection limit three weeks after infection. This coincides with an increase in parastic-specific serum IgG1 and IgG2 and a decrease of the antigen-specific IFN-gamma response in PP, PBMC and popliteal LN. We suggest a role for IFN-gamma and IL-12 in controlling the infection.

The use of a heterogeneously controlled mouse population reveals a significant correlation of acute phase parasitemia with mortality in Chagas disease.

Chagas disease develops upon infection with the protozoan parasite Trypanosoma cruzi and undergoes an acute phase characterized by massive parasite replication and the presence of parasites in the blood. This condition is known as acute phase parasitemia. This initial stage may result in a cure, in the development of the chronic stages of the disease or in the death of the infected host. Despite intensive investigation related to the characterization of the acute and chronic phases of the disease, the cause-effect relationship of acute phase parasitemia to the outcome of the disease is still poorly understood. In this study, we artificially generated a heterogeneously controlled mouse population by intercrossing F1 mice obtained from a parental breeding of highly susceptible A/J with highly resistant C57BL/6 mouse strains. This F2 population was infected and used to assess the correlation of acute phase parasitemia with the longevity of the animals. We used nonparametric statistical analyses and found a significant association between parasitemia and mortality. If males and females were evaluated separately, we found that the former were more susceptible to death, although parasitemia was similar in males and females. In females, we found a strong negative correlation between parasitemia and longevity. In males, however, additional factors independent of parasitemia may favor mouse mortality during the development of the disease. The correlations of acute phase parasitemia with mortality reported in this study may facilitate an appropriate prognostic approach to the disease in humans. Moreover, these results illustrate the complexity of the mammalian genetic traits that regulate host resistance during Chagas disease.

Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs

Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model.

Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs.

Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model.

Differential use of TLR2 and TLR9 in the regulation of immune responses during the infection with Trypanosoma cruzi.

Pathogens express ligands for several TLRs that may play a role in the induction or control of the inflammatory response during infection. Concerning Trypanosoma cruzi, the agent of Chagas disease, we have previously characterized glycosylphosphatidylinositol (GPI) anchored mucin-like glycoproteins (tGPI-mucin) and unmethylated CpG DNA sequences as TLR2 and TLR9 agonists, respectively. Here we sought to determine how these TLRs may modulate the inflammatory response in the following cell populations: F4/80(+)CD11b(+) (macrophages), F4/80(low)CD11b(+) (monocytes) and MHCII(+)CD11c(high) (dendritic cells). For this purpose, TLR2(-/-) and TLR9(-/-) mice were infected with Y strain of T. cruzi and different immunological parameters were evaluated. According to our previous data, a crucial role of TLR9 was evidenced in the establishment of Th1 response, whereas TLR2 appeared to act as immunoregulator in the early stage of infection. More precisely, we demonstrated here that TLR2 was mainly used by F4/80(+)CD11b(+) cells for the production of TNF-α. In the absence of TLR2, an increased production of IL-12/IL-23p40 and IFN-γ was noted suggesting that TLR2 negatively controls the Th1 response. In contrast, TLR9 was committed to IL-12/IL-23p40 production by MHCII(+)CD11c(high) cells that constitute the main source of IL-12/IL-23p40 during infection. Importantly, a down-regulation of TLR9 response was observed in F4/80(+)CD11b(+) and F4/80(low)CD11b(+) populations that correlated with the decreased TLR9 expression level in these cells. Interestingly, these cells recovered their capacity to respond to TLR9 agonist when MHCII(+)CD11c(high) cells were impeded from producing IL-12/IL-23p40, thereby indicating possible cross-talk between these populations. The differential use of TLR2 and TLR9 by the immune cells during the acute phase of the infection explains why TLR9- but not TLR2-deficient mice are susceptible to T. cruzi infection.

Expression profile of immune-related genes in Lates calcarifer infected by Cryptocaryon irritans.

Cryptocaryon irritans causes Cyptocaryonosis or white spot disease in a wide range of marine fish including Lates calcarifer (Asian seabass). However, the immune response of this fish to the parasite is still poorly understood. In this study, quantitative polymerase chain reaction (qPCR) was performed to assess the expression profile of immune-related genes in L. calcarifer infected by C. irritans. A total of 21 immune-related genes encoding various functions in the fish immune system were utilized for the qPCR analysis. The experiment was initiated with the infection of juvenile fish by exposure to theronts from 200 C. irritans cysts, and non-infected juvenile fish were used as controls. Spleen, liver, gills and kidney tissues were harvested at three days post-infection from control and infected fish. In addition, organs were also harvested on day-10 post-infection from fish that had been allowed to recover from day-4 up to day-10 post-infection. L. calcarifer exhibited pathological changes on day-3 post-infection with the characteristic presence of white spots on the entire fish body, excessive mucus production and formation of a flap over the fish eye. High quality total RNA was extracted from all tissues and qPCR was performed. The qPCR analysis on the cohort of 21 immune-related genes of the various organs harvested on day-3 post-infection demonstrated that most genes were induced significantly (p < 0.05) in all tissues, particularly liver (11/21 genes) and kidney (11/21). The expression profile demonstrated that induction of the MHC Class IIα gene was the highest compared to the other genes followed by serum amyloid A, CC chemokine and hepcidin-2 precursor genes. In fish that were allowed to recover from the C. irritans infection (10 days post-infection), expression of the immune-related genes was down-regulated to levels similar to the control fish. These results provide insights into the interaction between C. irritans and L. calcarifer and suggest that the innate immune system plays an important role in early defence against parasite infection allowing the fish to eventually recover from the infection.

Cryptocaryon irritans infection induces the acute phase response in Lates calcarifer: a transcriptomic perspective.

Cryptocaryoniasis (also known as marine white spot disease) is mediated by Cryptocaryon irritans. This obligate ectoparasitic protozoan infects virtually all marine teleosts, which includes Lates calcarifer, a highly valuable aquaculture species. Little is known about L. calcarifer-C. irritans interactions. This study was undertaken to gain an informative snapshot of the L. calcarifer transcriptomic response over the course of C. irritans infection. An in-house fabricated cDNA microarray slides containing 3872 probes from L. calcarifer liver and spleen cDNA libraries were used as a tool to investigate the response of L. calcarifer to C. irritans infection. Juvenile fish were infected with parasites for four days, and total RNA was extracted from liver tissue, which was harvested daily. We compared the transcriptomes of C. irritans-infected liver to uninfected liver over an infection period of four days; the comparison was used to identify the genes with altered expression levels in response to C. irritans infection. The greatest number of infection-modulated genes was recorded at 2 and 3 days post-infection. These genes were mainly associated with the immune response and were associated in particular with the acute phase response. Acute phase proteins such as hepcidin, C-type lectin and serum amyloid A are among the highly modulated genes. Our results indicate that an induced acute phase response in L. calcarifer toward C. irritans infection is similar to the responses observed in bacterial infections of teleosts. This response demonstrates the importance of first line defenses in teleost innate immune responses against ectoparasite infection.

IL-17 is necessary for host protection against acute-phase Trypanosoma cruzi infection.

IL-17A is a key cytokine that induces inflammatory responses through the organized production of inflammatory cytokines, such as IL-6, TNF-alpha, and GM-CSF, and induces neutrophil migration. The roles of IL-17A in infection of intracellular protozoan parasites have not been elucidated, although augmented immune responses by IL-17A are important for the resolution of some bacterial and fungal infections. Therefore, we experimentally infected IL-17A-deficient (IL-17A(-/-)) mice with Trypanosoma cruzi. IL-17A(-/-) mice had a lower survival rate and prolonged worse parasitemia compared with control C57BL/6 wild-type (WT) mice postinfection. In the infected IL-17A(-/-) mice, multiple organ failure was observed compared with WT mice, as reflected by the marked increase in serologic markers of tissue injury, such as aspartate aminotransferase, which resulted in increased mortality of IL-17A(-/-) mice. Expression of cytokines, such as IFN-gamma, IL-6, and TNF-alpha, was lower in liver-infiltrating cells from the IL-17A(-/-) mice compared with WT mice. A similar defect was observed in the expression of neutrophil enzymes, such as myeloperoxidase and lipoxygenase, whereas cellular infiltration into the infected tissues was not affected by IL-17A deficiency. These results suggested that the efficient activation of immune-related cells critical for the killing of T. cruzi was impaired in the absence of IL-17A, resulting in the greater susceptibility of those mice to T. cruzi infection. From these results, we conclude that IL-17A is important for the resolution of T. cruzi infection.

Low prevalence of an acute phase response in asymptomatic children from a malaria-endemic area of Papua New Guinea.

Levels of C-reactive protein (CRP), a classic marker for the acute phase response (APR), were measured in children with asymptomatic malaria infection in the Amele region of Papua New Guinea (PNG). Despite the presence of parasitemia, the prevalence of CRP levels consistent with an APR (CRP > 10 microg/mL) was very low (< 10%). Splenomegaly was significantly associated with increased parasitemia (P < 0.001) and CRP levels (P < 0.001), highlighting the importance of splenomegaly as an indicator of recent high density infection in this population. Multivariate analysis showed that CRP levels were significantly associated with splenomegaly, fever, hemoglobin, and age (P < or = 0.002). CRP levels also increased with increasing parasitemia (P < 0.001) but remained < 3.5 microg/mL. The low levels of CRP indicate that children in the Amele modulate inflammation associated with malaria.

Evidence of an acute phase response in dogs naturally infected with Babesia canis.

The erythrocyte sedimentation rate (ESR), white blood cell count (WBC), haematocrit (HCT) and platelet number (PLT) were quantified and compared with the acute phase proteins (APPs) in dogs naturally infected with Babesia canis and healthy dogs. Both groups were treated with imidocarb dipropionate on the day of admission and both groups were monitored for all parameters on the admission day and on the first, second, third, fourth and seventh days in order to determine the presence of an acute phase reaction, to assess the diagnostic value of these markers in uncomplicated canine babesiosis and to evaluate the use of APPs in treatment monitoring. It was demonstrated that an acute phase response occurs in dogs naturally infected with Babesia canis, with significant increases in the concentration of major acute phase proteins. The serum concentration of C-reactive protein (CRP), serum amyloid A (SAA) and the erythrocyte sedimentation rate (ESR) decreased daily after treatment and approached reference range values by the eighth day. PLT and haematocrit (HCT) increased daily after treatment and approached reference range values by the fourth day. WBC and haptoglobin increased after treatment and then decreased from the third and fourth days, respectively, to the eighth day. The diagnostic sensitivity of CRP, SAA and PLT was significantly higher compared to haptoglobin, ESR, HCT and the WBC count. CRP and SAA were of clinical use in monitoring the response to antibabesial treatment.

Evidence for a protective role of tumor necrosis factor in the acute phase of Trypanosoma cruzi infection in mice.

A possible role for tumor necrosis factor (TNF) alpha during Trypanosoma cruzi infection was explored by using transgenic mice expressing in blood high levels of a soluble TNFR1-FcIgG3 fusion protein, which neutralizes the effects of TNF in vivo. Nontransgenic littermates were used as controls. The transgenic mice showed high susceptibility to T. cruzi infection. Inocula sublethal for control mice resulted in over 80% mortality associated with higher levels of parasites in the blood. In histological sections of the hearts of transgenic mice, large parasitic clusters without inflammatory cell infiltrates around the parasites were seen, while smaller parasitic clusters associated with leukocytes were seen in control mice. No difference in specific antibody response or lymphocyte composition of the spleen was found between transgenic and control mice, although the unresponsiveness of spleen cells to concanavalin A stimulation in vitro, typical of the acute phase of T. cruzi infection, was less pronounced in transgenic mice. Infected transgenic mice produced higher levels of gamma interferon than did control mice. These results confirm that TNF is involved in mechanisms leading to parasite clearance and protection from death in the acute phase of T. cruzi infection. More importantly, the data reveal that TNF is necessary for the establishment of effective tissue inflammation and parasite load control in acute experimental Chagas' disease myocarditis.

Anthelminthic treatment raises plasma iron levels but does not decrease the acute-phase response in Jakarta school children.

The study was conducted to investigate the impact of intestinal helminthiasis and treatment on iron status and acute phase response (APR) among urban Indonesian primary school children, aged 8-11 years old. The prevalence of helminthiasis among these children was; Ascaris lumbricoides, 81.6%; Trichuris trichiura, 88.3%; and mixed infection of A. lumbricoides and T. trichiura, 70.0%. Of 120 children enrolled in the investigation, 59 received a single 400 mg dose of albendazole, and 61 received a placebo. Ten days following treatment, the prevalence of ascariasis and trichuriasis in the treatment group diminished to 0% and 27%, respectively, and in the placebo group to 63.9% and 68.9%. Plasma iron, hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) concentrations were determined prior to the intervention and 10 days after. Plasma iron concentrations and WBC count rose in the treatment group (p=< or =0.05) when compared to baseline status. Increases in hemoglobin concentrations observed in the treatment group 10 days post-treatment were not statistically significant. CRP, IL-1, IL-6 and TNF were found to be within normal limits for both groups both before and after treatment. ESR increased significantly in both treatment and placebo groups when compared the rates measured before treatment. These findings show that treatment with albendazole is associated not only with a decreased worm burden in school children, but also a rise in plasma iron.

Localization of alpha 2-macroglobulin protein and messenger RNA in rat liver fibrosis: evidence for the synthesis of alpha 2-macroglobulin within Schistosoma mansoni egg granulomas.

alpha 2-Macroglobulin (alpha 2M) in the rat is a strong-reacting acute-phase protein with potent protease-inhibiting and cytokine-binding properties. Production of alpha 2M is ascribed mainly to liver parenchymal cells. In the present study, we investigated, by means of immunohistochemistry and in situ hybridization, whether fibrosis in the rat liver induced by Schistosoma mansoni eggs leads to local production of alpha 2M. alpha 2M protein and messenger RNA (mRNA) in the unaffected liver tissue, as well as serum values of alpha 2M, were comparable in control rats and egg-injected rats, at 1, 3, and 8 weeks after injection of the eggs. alpha 2M was homogeneously distributed across the liver lobule. In contrast, at the sites of the granulomas, a strong increase in alpha 2M was observed. alpha 2M mRNA was expressed by granuloma cells, but not by the surrounding liver parenchymal cells. Within the granulomas, alpha 2M protein was present in numerous spindle-shaped cells and was diffusely distributed in the extra-cellular matrix. Using double-staining techniques, a subpopulation of the alpha 2M-positive cells in the granulomas appeared to be desmin-positive, suggesting a myofibroblast origin. In addition, parenchymal cells directly surrounding the granulomas contained alpha 2M protein in approximately 50% of the granulomas 1 week after injection of the eggs. In situ hybridization on consecutive sections revealed that these parenchymal cells showed only background activity of alpha 2M mRNA, suggesting uptake of alpha 2M-protein by these parenchymal cells and previous activation of alpha 2M by proteases within the granuloma. The significance of the present study is that alpha 2M is produced locally at sites of inflammation and liver fibrosis, without measurable increase of serum levels of alpha 2M. Unexpectedly, alpha 2M present at the sites of the granulomas is not produced by the liver parenchymal cells, but rather by granuloma cells.

Estudo dos níveis plasmáticos de alfa-macroglobulinas durante a fase aguda da infecção por Trypanosoma cruzi / Study of the plasma levels of alpha-macroglobulins during the acute phase of infection for Trypanosoma cruzi

Analisou-se a resposta de fase aguda (RFA) à infecção experimental por T. cruzi, através de estudos dos níveis plasmáticos de uma família de proteínas de fase aguda (PFA), as alfa-macroglobulinas (AM) em diversas cepas de camundongos. As AM são importantes inibidores fisiológicos de proteases, tendo também atividade imunomodulatória. Para a realização deste estudo foi fundamental a elaboração de um método de ELISA de inibição extremamente sensível, permitindo a detecção de AM em pequenos volumes de plasma. O desenvolvimento deste ELISA viabilizou o acompanhamento individualizado de animais controle e infectados e a comparação das respostas de animais resistentes e suscetíveis à infecção. Os resultados obtidos demonstram que as AM são importantes PFA em duas das três cepas de camundongos isogênicos estudadas. Ficou demonstrado ainda que os padrões de síntese de AM durante a fase aguda são diferentes nas diversas cepas estudadas, embora sejam homogêneos entre animais de umamesma cepa. Os resultados indicam que as AM atuam como PFA também em animais geneticamente heterogêneas, embora nestes casos o nível e a cinética de síntese de A2M sejam extremamente variáveis. Não se observou a existência de correlação entre níveis de AM e resistência ou susceptibilidade à fase aguda da infecção por T. cruzi. Resultados preliminares obtidos com pacientes durante a fase aguda da infecção por T. cruzi demonstraram que as AM atuam como PFA também na doença de Chagas e que a síntese destas proteínas em humanos apresenta uma heterogeneidade comparável àquela sugerida pelos estudos experimentais. O fato de que as AM têm função imunomodulatória, associado à heterogeneidade de sua síntese durante a fase aguda da infecção por T. cruzi, confirmam a importância de estudos posteriores abordando o eventual envolvimento das AM nos diversos desenvolvimentos da doença de Chagas em sua fase crônica.

Reaçäo de fase aguda e parasitismo na veia central da supra-renal de chagásicos crônicos / Acute-phase reaction and parasitism in the central adrenal vein in Chagas' disease patients

The systemic reaction to severe trauma and/or infection, acute phase response (APR), are often associated with immunosuppression and reactivation of chronic latent infection. Our main purpose was to verify, in a group of 71 autopsied chronic chagasic with or without APR, the frequency of T. cruzi nests in the central vein of adrenal gland (CVAG). APR, defined by: 1) death secondary to sepsis and/or trauma plus, 2) bleeding stress gastric ulcerations or 3) spleen reactional state or 4) liver steatosis, was observed in 30 chronic chagasic (APR+). Weight, height and body mass index (BMI) were obtained. APR(+) chronic chagasic had worse nutritional status than APR(-) ones: weight = 49.0 vs 54.5 kg; BMI = 17.5 vs 20.6 kg/m2 (median p < 0.05). CVAG T. cruzi nests frequency were similar (43.3 per cent and 43.9 per cent , respectively) between both Groups. We conclude that APR(+) chronic chagasic had worse nutritional status than APR(-) ones, and that APR development did not change the CVAG T. cruzi nests frequency

[Acute-phase reaction and parasitism in the central adrenal vein in Chagas' disease patients]. / Reação de fase aguda e parasitismo na veia central da supra-renal de chagásicos crônicos.

The systemic reaction to severe trauma and/or infection, acute phase response (APR), are often associated with immunosuppression and reactivation of chronic latent infection. Our main purpose was to verify, in a group of 71 autopsied chronic chagasic with or without APR, the frequency of T. cruzi nests in the central vein of adrenal gland (CVAG). APR, defined by: 1) death secondary to sepsis and/or trauma plus, 2) bleeding stress gastric ulcerations or 3) spleen reactional state or 4) liver steatosis, was observed in 30 chronic chagasic (APR+). Weight, height and body mass index (BMI) were obtained. APR(+) chronic chagasic had worse nutritional status than APR(-) ones: weight = 49.0 vs 54.5 kg; BMI = 17.5 vs 20.6 kg/m2 (median p < 0.05). CVAG T. cruzi nests frequency were similar (43.3% and 43.9%, respectively) between both Groups. We conclude that APR(+) chronic chagasic had worse nutritional status than APR(-) ones, and that APR development did not change the CVAG T. cruzi nests frequency.