Swine pericardium as dermal substrate for human keratinocyte culture.

BACKGROUND: Synthetic skin analogues or living allogeneic or autologous cells are used as dressings for the care of skin wounds, as well as temporary or permanent substitutes for damaged epithelia. OBJECTIVES: To evaluate if keratinocyte growth on a swine pericardium substrate mimics the natural epithelial layers compared with cultures on allogeneic dermis, which is accepted as having appropriate physical and chemical properties for growth and differentiation. METHODS: Keratinocytes were cultured on a swine pericardium substrate and allogeneic dermis, either submerged or at the air-liquid interface. At 7, 14 and 21 days postseeding the cultures were evaluated by light microscopy after both haematoxylin and eosin staining and immunohistochemistry. RESULTS: Cell-substrate interactions led to growth, stratification and differentiation of cells, with the definition of epithelial layers. The submerged system showed a continuous growth rise on both composites, but this was more prominent with the swine pericardium substrate. An increase in the number of layers at the air-liquid interface with the dermis composites, in contrast to the submerged cultures, occurred only from days 7 to 14. The pattern of keratinocyte growth on swine pericardium substrate was much better in the submerged than in the air-liquid interface cultures. CONCLUSIONS: The results indicate that swine pericardium is a better substrate than allogeneic dermis for keratinocyte cultures in submerged but not in air-liquid interface cultures. Swine pericardium as a substrate opens one more possibility for skin restoration after trauma or burns.

CD4 and CD8 distribution profile in individuals infected by Schistosoma mansoni.

RATIONALE: Patients with chronic Schistosoma mansoni infection show lower anti-soluble egg antigen (SEA) proliferation responses and higher responses to soluble worm antigen preparation (SWAP). OBJECTIVE: To compare the activation status and proliferation response of peripheral blood mononuclear cells (PBMC) of infected (XTO) and egg-negative individuals (NI) living in the same endemic area. METHODS: XTO (n = 51) and NI individuals from the same geographical area (n = 37) and healthy blood donors (n = 22) were evaluated before and after stimulation with SEA and SWAP. The expression of activation markers (CD4(+) HLADR(+), CD8(high+)HLA-DR(+) and CD8(+) CD28(+)) and proliferation assay was assessed by flow cytometry. FINDINGS: PBMC from infected patients showed lower frequency of CD4(+) but no change in CD8(+) T cells when compared with the healthy donor group. The ratio CD4(+)/CD8(+) was 1.3, 0.6 and 0.5 in healthy donors, infected and non-infected individuals, respectively. The HLA-DR(+) expression on CD8(+) was higher in PBMC from infected and non-infected individuals than from healthy donors, but similar in both total lymphocytes and CD4(+) populations. No intergroup proliferation response differences were observed in CD4(+) and CD8(+) PBMC unstimulated and stimulated with SEA and SWAP. The SEA but not SWAP-stimulated cells showed a decrease in the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2). CONCLUSIONS: XTO and NI individuals living in the same area presented a smaller per cent of CD4(+) and a higher per cent of CD8(+) cells. The activation by either CD8(high+)HLA-DR(+) or CD8(high+)HLA-DR(+)/CD8(+) was enhanced and decreased in XTO and NI by CD8(+) CD28(+) and CD8(+) CD28(+)/CD8(+) when compared with healthy donor. ERK phosphorylation was attenuated in XTO and NI individuals when stimulated with SEA but not SWAP.

Studies with transfected and permeabilized RBL-2H3 cells reveal unique inhibitory properties of protein kinase C gamma.

To characterize protein kinase C (PKC) gamma, an isozyme found exclusively in brain and spinal cord, its cDNA was introduced into basophilic RBL-2H3 cells that lack this isozyme. The expression of PKC gamma significantly attenuated antigen-induced responses including hydrolysis of inositol phospholipids, increase in cytosolic calcium, and secretion of granules but enhanced antigen-induced release of arachidonic acid. Instead of a sustained increase in cytosolic calcium, antigen now induced calcium oscillations; possibly as a consequence of suppression of the phospholipase C activity and incomplete emptying of internal calcium stores. In addition, PKC gamma appeared to inhibit activation of other PKC isozymes because phorbol 12-myristate 13-acetate failed to act synergistically with the Ca(2+)-ionophore on secretion. This was confirmed in other studies where PKC gamma was shown to suppress the transduction of stimulatory signals by other isozymes of PKC on provision of these isozymes to PKC-depleted permeabilized cells. The studies in total indicated that only PKC gamma was capable of inhibiting both early and distal signals for secretion including those signals transduced by endogenous isozymes of PKC.

Brazilian medical publications: citation patterns for Brazilian-edited and non-Brazilian literature.

Today, the quality of a scientific article depends on the periodical in which it is published and on the number of times the article is cited in the literature. In Brazil, the criteria for the evaluation of this scientific production are improving. However, there is still some resistance, with authors arguing that Brazilian publications must be preferentially addressed to the national readers and, therefore, they should ideally be written in Portuguese. In order to determine the kind of scientific journals cited in the reference lists of articles published in medical periodicals edited in Brazil, in the present study we determine the rate of Portuguese/English citations. Three issues of 43 periodicals (19 indexed in SciELO, 10 in PubMed, 10 in LILACS, and 4 in the ISI-Thompson base) of different medical specialties were analyzed, and the number of both Portuguese and English citations in the reference list of each article was recorded. The results showed that in Brazilian-edited journals the mean number of citations/article was 20.9 +/- 6.9 and the percentage of citations of international non-Brazilian periodicals was 86.0 +/- 11.2%. Of the latter, 94.4 +/- 7.0 are indexed by ISI-Thompson. Therefore, we conclude that Brazilian medical scientists cite the international non-Brazilian periodicals more than the national journals, and most of the cited papers are indexed by ISI-Thompson.

Receptor-mediated release of inositol 1,4,5-trisphosphate and inositol 1,4-bisphosphate in rat basophilic leukemia RBL-2H3 cells permeabilized with streptolysin O.

Antigen-mediated exocytosis in intact rat basophilic leukemia (RBL-2H3) cells is associated with substantial hydrolysis of membrane inositol phospholipids and an elevation in concentration of cytosol Ca2+ ([ Ca2+i]). Paradoxically, these two responses are largely dependent on external Ca2+. We report here that cells labeled with myo-[3H]inositol and permeabilized with streptolysin O do release [3H]inositol 1,4,5-trisphosphate upon stimulation with antigen or guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) at low (less than 100 nM) concentrations of free Ca2+. The response, however, is amplified by increasing free Ca2+ to 1 microM. The subsequent conversion of the trisphosphate to inositol 1,3,4,5-tetrakisphosphate is enhanced also by the increase in free Ca2+. Although [3H]inositol 1,4,5-trisphosphate accumulates in greater amounts than is the case in intact cells, [3H]inositol 1,4-bisphosphate is still the major product in permeabilized cells even when the further metabolism of [3H]inositol 1,4,5-trisphosphate is suppressed (by 77%) by the addition of excess (1000 microM) unlabeled inositol 1,4,5-trisphosphate and the phosphatase inhibitor 2,3-bisphosphoglycerate. It would appear that either the activity of the membrane 5-phosphomonoesterase allows virtually instantaneous dephosphorylation of the inositol 1,4,5-trisphosphate under all conditions tested or both phosphatidylinositol 4-monophosphate and the 4,5-bisphosphate are substrates for the activated phospholipase C. The latter alternative is supported by the finding that permeabilized cells, which respond much more vigorously to high (supraoptimal) concentrations of antigen than do intact RBL-2H3 cells, produce substantial amounts of [3H]inositol 1,4-bisphosphate before any detectable increase in levels of [3H]inositol 1,4,5-trisphosphate.

Helicobacter pylori and gastric histamine concentrations.

An enzyme isotopic assay was used to determine the histamine concentration in the gastric mucosa of patients positive for Helicobacter pylori with (n = 11) and without duodenal ulceration (n = 9) and in negative controls (n = 7). A significant difference was observed when the histamine content of H pylori negative subjects was compared with that of positive patients. On the other hand, there was no significant difference in histamine concentration between H pylori positive patients with duodenal ulceration and those without duodenal ulceration. H pylori positive patients with and without duodenal ulceration had significantly lower gastric histamine concentrations than H pylori negative subjects. The lower gastric histamine concentration observed in H pylori positive patients might be due to increased histamine release which could in turn induce increased gastric acid secretion.

Differential cellular reactivity to adult worm antigens of patients with different clinical forms of schistosomiasis mansoni.

Analysis of the proliferation in vitro of peripheral blood mononuclear cells and the production of interferon-gamma (IFN-gamma) in individuals infected with Schistosoma mansoni and showing different clinical forms of the disease, as well as normal putatively immune individuals from an endemic area, was undertaken using total and fractionated soluble adult worm antigens (SWAP). A higher frequency of detectable response to fractionated antigens in T cell Western blot assays was observed in individuals with the more severe forms of the disease. Analysis of variance showed that, in the Western blot assays, there was a statistically significant difference in the level of cellular proliferation to antigens with low molecular weight (less than 21 kDa) between hepatosplenic patients and those with intestinal and hepatointestinal forms of the disease. No correlation between cellular proliferation and IFN-gamma production was observed. Most of the normal individuals from an endemic area failed to show significant proliferative responses to SWAP T cell Western blot assays or to antigen immobilized on nitrocellulose; they did show significant proliferative responses to whole soluble SWAP with positive IFN-gamma production. The results are consistent with the hypothesis that variations in the cellular immune responses to SWAP influence both the development of pathology and resistance to infection in schistosomiasis mansoni.

On the increase of portal pressure during the acute and chronic phases of murine schistosomiasis mansoni and its reversibility after treatment with oxamniquine.

The purpose of the present study was to evaluate the effect of treatment with oxamniquine on the portal pressure of mice infected with Schistosoma mansoni. The animals were infected with 30 cercariae and portal pressure was measured with a polygraph at 70 (acute phase) and 160 (chronic phase) days after infection. On days 70 and 160 two other groups of infected mice were treated with 400 mg/kg of oxamniquine and portal pressure was measured 90 days later (160 and 250 days after infection). A group of uninfected mice was used as control. The measured portal pressures, in mmHg, were: matched uninfected control mice 8.7+/-2.1 and acute phase group, measured at day 70, 13.4+/-3.5. Matched uninfected control 7.5+/-0.6 and chronic phase group, measured at day 160 post-infection, 11.6+/-1.5. Matched uninfected mice 6.9+/-0.9 and chronic phase group, measured at day 250, 10.4+/-1.8. Oxamniquine-treated at day 70 and measured at day 160 7.9+/-0.4; oxamniquine-treated at day 160 and measured at day 250, 7.6+/-1.7. The infection of mice with 30 cercariae of S. mansoni induced portal hypertension, both during the acute and chronic phases and treatment with oxamniquine caused portal pressure to return to normal levels.

Effect of scorpion toxin from Tityus serrulatus on the contraction of the isolated rat uterus.

Scorpion toxin T1 from Tityus serrulatus was tested for its effects on the isolated rat uterus preparation. T1 (5 micrograms/ml) caused a contraction of the uterus, which was potentiated by neostigmine (1.64 x 10(-6) M) and abolished by atropine (1.4 x 10(-7) M). After addition of neostigmine to the bath, we noted a higher amplitude of the toxin-induced contractions, and the appearance of repetitive rhythmic contractions. The scorpion toxin-induced contraction was not prevented by previous addition to the bath of hexamethonium or bradykinin, 5-HT and angiotensin II antagonists. The uterine contraction was prevented by previous addition to the bath of either tetrodotoxin (5 x 10(-8) M) or lidocaine (4.2 x 10(-5) M). These data seem to indicate that scorpion toxin-induced rat uterus contractions are due to actions on post-ganglionic autonomic nerve endings, with acetylcholine release and stimulation of muscarinic receptors.

Effects of purified scorpion toxin (tityustoxin) on gastric secretion in the rat.

An i.v. bolus injection of a purified scorpion toxin (tityustoxin, TsTX) in urethane anesthetized rats induced a dramatic increase in volume, acid and pepsin output of gastric juice and a significant decrease in its pH. The maximal stimulatory effects of TsTX on gastric secretion were obtained with a dose of 0.25 mg/kg acting for 60 min. Hexamethonium did not prevent the gastric secretion evoked by TsTX, whereas atropine or cimetidine abolished partially or totally the toxin effects. Acute bilateral cervical or abdominal vagotomy did not prevent the effects of TsTX on gastric secretion, but chronic abdominal vagotomy abolished the toxin effects. Chronic antrectomy diminished the effect of TsTX on gastric secretion. In the pylorus-ligated group of rats, the gastric secretion evoked by TsTX was not different from that observed in the pylorus-intact group. It is concluded that the changes in gastric volume, acid output, pH and pepsin output induced by TsTX in the rat are due to the release of chemical mediators from postganglionic autonomic nerve fibers which would act through muscarinic and H2-receptors stimulation.

Cardiovascular and respiratory effects induced by a purified scorpion toxin (tityustoxin) in unanesthetized rats.

Intravenous injection of a purified scorpion toxin (tityustoxin) into unanesthetized rats induced acute pulmonary edema, which was directly related to the dose and the time of intoxication. To study the cardiovascular and respiratory effects evoked by an edematogenic dose of the toxin (1 mg/kg), the following parameters were recorded in unanesthetized rats: systolic, diastolic and mean arterial pressure; central venous pressure; electrocardiogram; respiratory movements. The toxin induced acute systolic and diastolic hypertension, bradycardia and bradypnea. During a 1 hr period, the systolic, diastolic and mean arterial pressure fell progressively to control values, whereas the central venous pressure did not change significantly. The cardiac and respiratory rates remained lower than the control values during a 1 hr period. Several changes in the respiratory pattern were recorded, such as gasping, prolonged and labored expiration, ataxic rhythm and noisy inspiration with the mouth open. These respiratory changes were explained, in part, by the presence of edema in the lungs and froth in the trachea. From a group of 24 rats, 6 died 18-30 min after tityustoxin injection. The cause of death was apnea. The female rats were more susceptible to pulmonary edema and death than the male rats.

Effect of Tityus serrulatus scorpion toxin on serum gastrin levels in anaesthetized rat.

Scorpion toxin induces gastric secretion of acid and pepsin in rats. These effects seem to be mediated by the release of acetylcholine and histamine. However, the role of gastrin in the scorpion-toxin-induced gastric secretion is unknown. We describe the effects of the T1 fraction purified from Tityus serrulatus scorpion venom on serum and on antral tissue gastrin levels in anaesthetized rats. Gastrin levels in serum and in the antral mucosa were measured before and at intervals 5, 15, 30, 60, 90 up to 120 min after the intravenous injection of saline or the T1 fraction of scorpion venom (0.25 mg/kg) into anaesthetized rats. Antral G-cells were submitted to immunocytochemistry and electron microscopy. The data on gastrin were correlated with the gastric juice volume, and the acid and pepsin output increases induced by toxin. Scorpion toxin induced a significant increase in volume, acid output and pepsin output of gastric juice and gastrin serum levels 15-60 min after injection. Simultaneous measurements of antral gastrin levels did not show significant effects. The number of dense, intermediate and empty granules per microm(2) in the cytoplasm of antral G-cells was not significantly changed 60 min after saline or toxin injection. Scorpion toxin significantly increased serum gastrin; levels in rats.

Acute gastric mucosal injury induced by toxins from Tityus serrulatus scorpion venom: a novel experimental model in the rat.

The effect of a partially purified fraction (T1) and toxin gamma purified from Tityus serrulatus scorpion venom, on gastric mucosa were investigated in anesthetized rats. The animals were injected i.v. with the T1 fraction (37.5 micrograms/100 g) or with saline and 60 min later were sacrificed and the stomachs resected. The gastric juice was measured and stereoscopic examination of the stomachs made. In animals injected with the T1 fraction there was an increase in volume, acidity and pepsin output of rat stomach. The T1 fraction also induced acute gastric injuries in the glandular mucosa, consisting of circular or linear ulcers, and punctiform lesions. Intravenous injection of 20 micrograms/100 g of a pure toxin obtained from Tityus serrulatus scorpion venom (toxin gamma) also induced similar lesions in the rat stomach. Our data indicate that the injection of T1 fraction or toxin gamma are good models to induce acute gastric ulcers in a short period of time in anesthetized rats.

Acid-base balance following Tityus serrulatus scorpion envenoming in anaesthetized rats.

In the present work the pH and arterial blood gases were measured in fasted and fed male albino rats, weighing 297 +/- 13 g, anaesthetized with urethane (1.4 g/kg, i.p.) before and after injection of T1 fraction from Titys serrulatus scorpion venom, during 60 min. Arterial blood samples were collected at 0, 5, 15, 30 and 60 min for pH, pCO2, pO2, bicarbonate and base-excess analysis. The data showed that the scorpion toxin induced a continuous drop in the blood pH along the time. Hypercapnia and hypoxemia peaking at 30 min and followed by a recovery towards normal values at 60 min were also observed. A pronounced decrease in the blood bicarbonate levels at 60 min and negative base-excess values along with time were evident at 60 min. The comparisons between fasted and fed animals have shown that in the last group the effects of scorpion toxin on the arterial blood gases were less pronounced. We conclude that T1 fraction of Tityus serrulatus scorpion venom induces in anaesthetized rats an acute respiratory acidosis followed by metabolic acidosis.

Serum levels of cytokines in patients envenomed by Tityus serrulatus scorpion sting.

Seventeen patients stung by Tityus serrulatus scorpion were classified as mild (pain at the site of the sting, n = 6), moderate (local pain and one of the following manifestations: vomiting, psychomotor agitation, prostration, sweating, tachypnea, tachycardia and mild arterial hypertension, n = 10) and severe cases (equal moderate cases plus cardiac failure, pulmonary edema and shock, n = 1). Venous blood was sampled for biochemical and hematological analysis and for IL-1alpha, IL-6, IL-10, TNF-alpha, IFN-gamma and GM-CSF ELISAs at the time of hospital admission, 6 h (moderate and severe cases), and 12, 18, 36 and 72 h (severe case) later. Ten age-matched healthy volunteers were used as control. Increased serum levels of IL-1alpha was noticed in all patients, high levels of IL-6, IFN-gamma and GM-CSF were observed only in a patient with severe envenomation. Our data suggest that a systemic inflammatory response-like syndrome is triggered during severe envenomation caused by T. serrulatus sting and that release of cytokines may be involved in this response.

The Bezold-Jarisch-like effect induced by veratridine and its potentiation by scropion toxin in the rat.

The Bezold-Jarisch-like effect (BJE) induced by 2.5 micrograms/100 g of veratridine injected intravenously or into the left ventricle was studied in anesthetized rats. The possible potentiation of the effect by a small dose (10 micrograms/100 g) of a purified scorpion toxin (tityustoxin) was also investigated. Heart rate (HR), electrocardiogram (ECG), mean arterial pressure (MAP) and respiratory rate (RR) were recorded. Intravenous (iv) injection of veratridine induced a BJE consisting of slight bradycardia in 4 out of 8 experiments, fall of MAP (from 107 +/- 3 to 90 +/- 4 mmHg) and apnea. The control RR was 105 +/- 5 insp/min and apnea, after veratridine, lasted 8 +/- 2 s. The BJE evoked by injection of a second dose of veratridine was potentiated 20 min after an iv injection of tityustoxin. The HR decreased from 334 +/- 16 to 108 +/- 17 beats/min, the MAP fell from 110 +/- 5 to 68 +/- 4 mmHg and the control RR of 92 +/- 5 insp/min was followed by a long period of apnea (68 +/- 17 s). Injection of veratridine into the left ventricle (lv) evoked a BJE characterized by slight bradycardia in 5 out of 10 experiments, arterial hypotension (from 110 +/- 6 to 89 +/- 6 mmHg) and tachypnea (from 82 +/- 6 to 102 +/- 7 insp/min). The effects induced by a second dose of veratridine were potentiated 20 min after an lv injection of tityustoxin. The HR decreased from 377 +/- 14 to 119 +/- 18 beats/min, the MAP fell from 119 +/- 5 to 72 +/- 10 mmHg and the RR increased from 80 +/- 6 to 117 +/- 9 insp/min. This tachypnea was followed by bradypnea 20 s later (21 +/- 6 insp/min). The ECG showed that hypotension induced by iv or lv injections of veratridine coincided with a slight sinus bradycardia before tityustoxin (N = 9) and A-V block after the toxin (N = 18). Cervical bilateral vagotomy prevented the cardiac and respiratory effects induced by lv veratridine in tityustoxin-treated rats, but a slight hypotension was still recorded (from 114 +/- 10 to 94 +/- 10 mmHg, P less than 0.05). Injection of veratridine (2.5 micrograms/100 g) into the ascendent aorta evoked a slight hypotension (from 105 +/- 6 to 87 +/- 7 mmHg, P less than 0.05) and tachypnea followed by bradypnea, but bradycardia was not recorded.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of scorpion toxin on gastric histamine and acetylcholine content in the rat.

1. The effects of a purified scorpion toxin (obtained from the Tityus serrulatus venom) on gastric secretion and on histamine and acetylcholine (ACh) levels were studied in rats. 2. Intravenous injection of 0.25 mg/kg of scorpion toxin induced a marked increase in gastric secretion in anesthetized rats. 3. Scorpion toxin also increased the histamine content in both the glandular and membranous portions of gastric wall, but there was no change in ACh content. 4. Incubation of slices of gastric wall with scorpion toxin induced a release of ACh from glandular and membranous portions. No effect of the toxin was observed on tissue-bound ACh or on free and tissue-bound histamine of either portion of the gastric wall. 5. We conclude that the gastric secretion evoked by intravenous injection of scorpion toxin in the rat is due, at least in part, to release of ACh and histamine. It is suggested that the toxin also induces synthesis of both ACh and histamine in the gastric wall.

Gastric acetylcholine and histamine content of normal and Trypanosoma cruzi-infected rats.

1. The consequences of acute Trypanosoma cruzi infection for acetylcholine and histamine levels in gastric wall and for mast cells of the stomach were studied in rats. 2. Intraperitoneal infection with 4,000 trypomastigotes/g of a Y strain of Trypanosoma cruzi led to a 4-fold decrease in gastric acetylcholine level and to a 57- and 15-fold increase in histamine content in the membranous and glandular regions of the rat stomach, respectively. 3. Infection of rats with Trypanosoma cruzi also induced a 2- and 4-fold increase in mast cell numbers in the membranous and glandular regions of the muscle layer of the gastric wall, respectively, and a ganglionic inflammatory reaction with predominance of mononuclear cells. 4. We conclude that in acutely Trypanosoma cruzi-infected rats, the reduction of acetylcholine content is due to gastric denervation and that the histamine increase might be secondary to gastric denervation and/or to an increase in the number of mast cells of the gastric wall.

Inhibition of gastric emptying and intestinal transit in anesthetized rats by a Tityus serrulatus scorpion toxin.

The effects of a fraction (T1) of Tityus serrulatus scorpion venom prepared by gel filtration on gastric emptying and small intestinal transit were investigated in male Wistar rats. Fasted animals were anesthetized with urethane, submitted to tracheal intubation and right jugular vein cannulation. Scorpion toxin (250 microg/kg) or saline was injected iv and 1 h later a bolus of saline (1.0 ml/100 g) labeled with 99m technetium-phytate (10 MBq) was administered by gavage. After 15 min, animals were sacrificed and the radioactivity remaining in the stomach was determined. Intestinal transit was evaluated by instillation of a technetium-labeled saline bolus (1.0 ml) through a cannula previously implanted in the duodenum. After 60 min, the progression of the marker throughout 7 consecutive gut segments was estimated by the geometric center method. Gastric retention of the liquid test meal in rats injected with scorpion toxin (median: 88%; range: 52-95%) was significantly higher (P<0.02) than in controls (54%; 21-76%), an effect which was not modified by gastric secretion blockade with ranitidine. The progression of the isotope marker throughout the small intestine was significantly slower (P<0.05) in rats treated with toxin (1.2; 1.0-2.5) than in control animals (2.3; 1.0-3.2). Inhibition of both gastric emptying and intestinal transit in rats injected with scorpion toxin suggests an increased resistance to aboral flow, which might be caused by abnormal neurotransmitter release or by the local effects of venom on smooth muscle cells.

Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection.

The role of different cytokines in the peripheral blood mononuclear cell (PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals "naturally" resistant to infection named normal endemic (NE). The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients. Similar results were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS. In contrast, the addition of anti-IL-10 antibodies to PBMC cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion. Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used. Analysis of IFN-gamma in the supernatants showed that PBMC from INT patients secreted low levels of IFN-gamma upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-gamma. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-gamma may be associated with resistance to infection.