Increase In Eosinophil Count Research Articles

Flowers in a bone marrow aspiration

An 18-year-old man from a rural area of Iran, Fars province, presented with fever of unknown origin (FUO) since 1 month prior to admission. On admission, temperature was 38.68C, blood pressure 110/70 mmHg, pulse rate 90 per min, and respiration rate 18 per min. Fever was double quotidian, and was accompanied by profuse sweating. Physical examination revealed a palpable spleen 3–4 cm below the left subcostal margin. There was neither lymphadenopathy nor hepatomegaly. Liver tests show a mild elevation in enzymes as follows: SGOT 49 Iu/L (up to 46 Iu/L), SGPT 50 Iu/L (up to 49 Iu/L), alkaline phosphatase 250 Iu/L (100–290 Iu/L), total protein 7.0 g/dL (5.5–8.0 g/dL), albumin 2.8 g/dL (3.2–5.6 g/dL), g-globulin 4.2 g/dL (2.2–3.5 g/ dL). Complete blood test shows a mild anemia as follows: hemoglobin 11.1 g/dL (13.5–17.5 g/dL), hematocrit 34.2% (41–53%), RBC count 3.89 3 1012/L (4.5–5.9 3 1012/L), WBC count 7.6 3 109/L (4.4–11 3 109/L), platelet count 282 3 109/L (150–450 3 109/L), reticulocyte count 2.1% (0.5–1.5%). C-reactive protein was 34 mg/dL, and erythrocyte sedimentation rate 51-mm/hr. Chest X-ray and electrocardiogram were normal. An abdominal ultrasound confirmed the splenomegaly. Tuberculin skin test and serological tests for syphilis, brucella, CMV, EBV, HIV, and hepatitis viruses were negative. Bone marrow aspiration revealed mild erythroid hyperplasia and a slight increase in eosinophil count; but the obvious finding in bone marrow was numerous Leishman bodies (amastigotes). Surprisingly, amastigotes were mostly in aggregates, forming different shapes resembling as follows: tear drop (Image 1A), clover leaf (Image 1B), ball (Image 1C), sunflowers (Image 1D,E), rossetes (Image 1F), ring and doughnut (Image 1G–I). Such aggregation has not been reported in lymph node aspiration or skin smears [1,2]. The patient received glucantim injections, which subsided the fever within the first week and splenomegaly regressed in the second week. The human stage amastigote is an obligate intracellular parasite, spherical, 2–5 lm in diameter, and displays a nucleus and kinetoplast. Human infection occurs by the bite of the Phlebotomus sandfly and injection of promastigote form into the subcutaneous tissue. They develop into the amastigote form and disseminate through the reticuloendothelial system. Visceral leishmaniasis (kala-azar) (VL) is caused by Leishmania donovani or Leishmania infantum [3]. In Iran, kala-azar mainly occurs in infants and children (infantile kala-azar) and shows a seasonal pattern, appearing from April to October with infection having taken in previous fall [3]. Children 1 to 4 years old are mainly affected. It occurs very rarely in adults. The clinical infection is characterized by chronic fever and hepatosplenomegaly. VL can rarely present with Evans syndrome [4]. The demonstration of the parasite is necessary for the diagnosis of kala-azar. The indirect fluorescent antibody and polymerase chain reaction tests and culture are also helpful in diagnosis. The treatment of choice is meglumine antimoniate (glucantime), given intramuscularly daily for 30 days (10 mg/kg of body weight). Residual spraying with DDT and use of mosquito nets during sleep are recommended to stop transmission by sandflies. VL occurs sporadically in the different geographic areas of Iran [3].

Role of Local Immunoglobulin E Specific for Alternaria alternata in the Pathogenesis of Nasal Polyposis

The role of fungal pathogens in the etiology of nasal polyposis remains unclear. The aim of this study was to determine whether there was a correlation between the presence of Alternaria-specific immunoglobulin (Ig)E antibodies, eosinophilic inflammation, and the development of nasal polyps. Prospective study. Serum and nasal tissue homogenates from 21 patients with manifestations of chronic sinusitis with nasal polyps were compared with specimens from 13 chronic sinusitis patients without polyps and 8 healthy controls. The Phadia ImmunoCAP and enzyme-linked immunosorbent assay were used to quantify levels of total IgE and Alternaria-specific (IgE, IgG, and IgA) antibodies. Eosinophil cationic protein (ECP) and tryptase levels were measured in tissue homogenates, whereas the inflammatory response was evaluated using tissue eosinophil counts in tissue samples. Serum analysis revealed no difference in the levels of total IgE and Alternaria-specific IgE, IgG, and IgA antibodies between the study groups. In contrast, the levels of Alternaria-specific IgE in tissue with polyps were significantly higher than in nonpolyp tissue. Increases in total tissue IgE paralleled increased levels of Alternaria-specific IgG and IgA antibodies in chronic sinusitis with nasal polyps as compared with control groups. A positive correlation was found between Alternaria-specific IgE and ECP in tissue. Increased mean levels of ECP corresponded to increased eosinophil counts in the group of patients with polyps. Alternaria-specific IgE and eosinophilic inflammation in nasal tissue correlates with the incidence of nasal polyps irrespective of specific IgE antibodies in serum. Together, the correlation between the local immune responses and the eosinophilic inflammation in nasal polyps suggests a possible role of Alternaria in the pathogenesis of nasal polyposis.

Safe Use of Meropenem in a Patient with a Possible Nonimmediate Allergy to Imipenem

Strong data are lacking on the cross-reactivity between individual carbapenems. We describe a 48-year-old woman with ventilator-associated Pseudomonas aeruginosa pneumonia who received an 8-day course of imipenem-cilastatin and experienced a delayed (i.e., nonimmediate) hypersensitivity reaction, evidenced by an extensive erythematous macular morbilliform rash and an increased eosinophil count. Eight days after completion of therapy, the pneumonia returned, and it was decided to avoid using imipenem-cilastatin; she was administered a 14-day course of meropenem. To our knowledge, this is the first report of a nonimmediate hypersensitivity reaction to imipenem-cilastatin without cross-reactivity to meropenem. This suggests that if carbapenem therapy is unavoidable, meropenem may be cautiously administered in patients with a known allergy to imipenem-cilastatin.

A Survey about Irritable Bowel Syndrome in South Korea

The aims of the present study were: (1) to assess the prevalence of symptom-based irritable bowel syndrome (IBS) in Korean adults, (2) to assess several organic abnormalities which can be found in IBS patients, and (3) to analyze the risk or associated factors that influence the presence of IBS. Adult health examinees were requested to fill out a questionnaire. The prevalence of IBS was calculated using Rome II criteria. Using several tests, several organic abnormalities were identified in the IBS group. Risk factors were analyzed by comparing the IBS and normal groups. The prevalence value for IBS according to Rome II criteria was 16.8%. Mucosal hyperplasia, lymphocyte aggregation, and increased eosinophil counts were relatively common microscopic findings in IBS group. Female gender, self-consciousness of IBS, and irregular defecation were expressed as significantly independent risk or associated factors for IBS. Several colonic microscopic findings mentioned above may be helpful in accurate diagnosis of IBS. Therefore a more-precise and large population study about these findings is necessary to reach a definitive conclusion.

Polymorphisms in IL13, total IgE, eosinophilia, and asthma exacerbations in childhood

It is unclear whether single nucleotide polymorphisms (SNPs) in the gene for IL-13 (IL13) influence asthma severity and/or asthma morbidity. To examine the relation between IL13 SNPs and asthma-related phenotypes in 2 independent populations. We used family-based methods to test for association between SNPs in IL13 and asthma-related phenotypes in Costa Rican children with asthma. We attempted to reproduce significant findings in white (non-Hispanic) children with asthma in the Childhood Asthma Management Program (CAMP). In Costa Rica and in CAMP, the A allele (Gln) of IL13 coding SNP (rs20541) was significantly associated with increased eosinophil count (P < .011 in both studies) and increased serum total IgE (P < .054 in both studies). The T allele of IL13 promoter SNP (rs1800925) was inversely associated with asthma exacerbations in Costa Rica (P = .069). Although this SNP (rs1800925) was not associated with asthma exacerbations among all white children in CAMP, it was associated with increased risk of asthma exacerbations among children on inhaled corticosteroids (P = .02). Polymorphisms in IL13 were significantly associated with serum total IgE and eosinophil count in 2 populations. IL13 polymorphisms may also be associated with asthma exacerbations, and this effect may be dependent on medication use. Our study is the first to report a potential negative interaction between a genetic polymorphism and response to inhaled corticosteroids. Polymorphisms in IL13 are associated with serum total IgE and eosinophil count and may be associated with asthma exacerbations.

Presentation and management of allergic fungal sinusitis.

To assess the presentation of allergic fungal sinusitis and describe the line of management in our setup. Descriptive study. Study was conducted in Otorhinolaryngology Department, Dow Medical College and Civil Hospital, Karachi, from January 2004 to January 2005. Culture and sensitivity / fungal stain proven 20 cases of allergic fungal sinusitis were selected for the study, irrespective of age and gender. Data including age, gender, socioeconomic status, signs, symptoms, laboratory findings (especially Immunoglobulin E and eosinophil count) and imaging studies (Computed Tomography and /or Magnetic Resonance Imaging) were noted for the study. Pre and postoperative medical treatment, surgery performed, follow-up; residual/recurrence disease and revised surgery performed were also recorded. In this series, allergic fungal sinusitis was a disease of younger age group with an average age of 20.75 years with male dominance (70%). Poor socioeconomic status (80%), allergic rhinitis (100%) and nasal polyposis (100%) were important associated factors. Nasal obstruction (100%), nasal discharge (90%), postnasal drip (90%) and unilateral nasal and paranasal sinuses involvement (60%) were the commonest presenting features. Aspergillus (60%) was the most common etiological agent. In all cases (100%), increased eosinophil count and IgE levels were present. Orbital (20%) and intracranial (10%) involvement were also seen. Surgical management was preferred in all cases. Functional endoscopic sinus surgery in 90% cases and lateral rhinotomy in 10% cases were performed. Recurrence / residual disease was seen in 20% cases. In this series, allergic fungal sinusitis was seen in immunocompetent, young males, belonging to poor socioeconomic status, suffering from allergic rhinitis and nasal polyposis, presenting with nasal obstruction, nasal discharge and postnasal drip. Functional endoscopic sinus surgery was the most important problem solving procedure while lateral rhinotomy was reserved for extensive disease.

Acute Eosinophilic Pneumonia Caused by CalciumStearate, an Additive Agent for an Oral Antihistaminic Medication

A 70-year-old man was admitted to our hospital because of dyspnea after taking an antihistaminic agent (homochlorcyclizine hydrochloride) for itching. Chest roentgenogram showed infiltration in the left lung field, and laboratory data revealed eosinophilia. Examination of the bronchoalveolar lavage fluid revealed an increased eosinophil count. A drug lymphocyte stimulation test was positive only for calcium stearate, an additive contained in the homochlorcyclizine hydrochloride tablet. The pulmonary infiltration and clinical symptoms subsided after withdrawal of all drugs and initiation of glucocorticoid therapy. Therefore, we concluded that this patient's pulmonary disease was caused by calcium stearate, an additive for an antihistaminic drug. An allergic reaction to a drug's additive material should be considered as a rare cause of drug-induced acute eosinophilic pneumonia.

Effects of protein supply and reproductive status on local and systemic immune responses to Teladorsagia circumcincta in sheep

The effects of protein supply and reproductive status on circulating antibody responses and local inflammatory cell counts were investigated in parasitized sheep, with local immune responses assessed through a recently refined abomasal cannulation methodology. We hypothesized that if breakdown of immunity has a nutritional basis, then protein scarcity would result in a breakdown of immunity to Teladorsagia circumcincta in both periparturient and non-reproducing (barren) ewes. Twin-bearing and barren, abomasally cannulated ewes were fed at either 0.8 or 1.3 times protein requirements from 3 weeks before until 6 weeks after parturition ( n = 6). All sheep were trickle infected at a rate of 10,000 infective larvae (L 3) per day, for 3 days per week throughout the experiment. Faecal egg counts remained virtually zero in all barren ewes, whilst protein supplementation reduced faecal egg counts in the periparturient ewes during most of the periparturient period. Final worm burdens, taken at 6 weeks into lactation, were lower for the barren ewes than for the lactating ewes, whilst protein supplementation reduced worm burdens in the latter. Protein supply did not affect mucosal mast cell counts, which were consistently higher for the barren ewes than the periparturient ewes, but were temporarily decreased around parturition. Barren ewes and protein supplemented lactating ewes had higher globule leukocyte counts than the unsupplemented lactating ewes. Protein supplementation increased eosinophil counts in the lactating ewes though only during the later part of the lactation period. Plasma IgA anti-L 3 antibody was similar for all ewes, but IgE anti-L 3 antibody was higher for the protein supplemented periparturient ewes compared to the unsupplemented periparturient ewes and all barren ewes. It is likely that the combination of low protein requirements and large body protein reserves did not result in breakdown of immunity to T. circumcincta for the barren ewes. These results suggest that changes in mucosal mast cell and eosinophil counts are not necessarily associated with changes in host resistance to T. circumcincta. However, the data support the view that increased globule leukocyte counts and plasma IgE anti-L 3 antibody may be associated with nutritionally improved expression of immunity in periparturient ewes.

Tissue eosinophilia: a morphologic marker for assessing stromal invasion in laryngeal squamous neoplasms

BackgroundThe assessment of tumor invasion of underlying benign stroma in neoplastic squamous proliferation of the larynx may pose a diagnostic challenge, particularly in small biopsy specimens that are frequently tangentially sectioned. We studied whether thresholds of an eosinophilic response to laryngeal squamous neoplasms provides an adjunctive histologic criterion for determining the presence of invasion.MethodsEighty-seven(n = 87) cases of invasive squamous cell carcinoma and preinvasive squamous neoplasia were evaluated. In each case, the number of eosinophils per high power field(eosinophils/hpf), and per 10 hpf in the tissue adjacent to the neoplastic epithelium, were counted and tabulated. For statistical purposes, the elevated eosinophils were defined and categorized as: focally and moderately elevated (5–9 eos/hpf), focally and markedly increased(>10/hpf), diffusely and moderately elevated(5–19 eos/10hpf), and diffusely and markedly increased (>20/10hpf).ResultsIn the invasive carcinoma, eosinophil counts were elevated focally and /or diffusely, more frequently seen than in non-invasive neoplastic lesions. The increased eosinophil counts, specifically >10hpf, and >20/10hpf, were all statistically significantly associated with stromal invasion. Greater than 10 eosinophils/hpf and/or >20 eosinophils/10hpf had highest predictive power, with a sensitivity, specificity and positive predictive value of 82%, 93%, 96% and 80%, 100% and 100%, respectively. Virtually, greater than 20 eosinophils/10 hpf was diagnostic for tumor invasion in our series.ConclusionOur study suggests for the first time that the elevated eosinophil count in squamous neoplasia of the larynx is a morphologic feature associated with tumor invasion. When the number of infiltrating eosinophils exceeds 10/hpf and or >20/10 hpf in a laryngeal biopsy with squamous neoplasia, it represents an indicator for the possibility of tumor invasion. Similarly, the presence of eosinophils meeting these thresholds in an excisional specimen should prompt a thorough evaluation for invasiveness, when evidence of invasion is absent, or when invasion is suspected by conventional criteria in the initial sections.

Role of gender and hormone-related events on IgE, atopy, and eosinophils in the Epidemiological Study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy

Background The pattern of asthma over the lifespan is different in male and female patients, but etiologic differences according to gender are only partially understood. In women, information regarding factors explaining perimenstrual asthma and the role of hormone-related aspects on asthma-related phenotypes is scanty. Objective To assess the relationships of eosinophils, IgE, and atopy with (1) asthma according to gender and age of onset and (2) hormone-related events. Methods Using data from the Epidemiological study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness and Atopy, adults and children with asthma recruited in chest clinics (n = 313) and first-degree relatives of patients with asthma (n = 214) were compared with nonasthmatic controls (n = 334) and first-degree relatives without asthma (n = 595). Results Among asthmatic women, eosinophilia was significantly associated with perimenstrual asthma independently from age, smoking, and asthma severity (eosinophils/mm 3 330 vs 194; P = .01). In nonasthmatic women, IgE level was significantly decreased (by half) and atopy decreased with menopause, and IgE increased with oral contraceptive use, independently from age and smoking. Considering both genders, the increase of eosinophil counts with asthma was significantly greater in women with childhood-onset asthma than in women with adulthood-onset or in men in general. No interaction between gender and asthma was observed for eosinophils in children and for IgE level and atopy in children and adults. Conclusion Results suggest a role of hormone-related events on asthma-related traits and support the hypothesis of the role of eosinophils in the persistence and severity of asthma.

Chronic Sinusitis with Nasal Polyps: Staphylococcal Exotoxin Immunoglobulin E and Cellular Inflammation

The etiology of chronic sinusitis with nasal polyposis (CS/NP) remains enigmatic. Frequently, Staphylococcus aureus is present in the nose of CS/NP patients, although the significance is unclear. Recent reports have suggested the hypothesis that these bacteria may secrete exotoxins triggering the inflammatory mucosal changes seen in CS/NP. This mechanism of immunopathology has been established in other diseases associated with Staphylococcus colonization and exotoxin secretion such as atopic dermatitis. In atopic dermatitis, the exotoxins incite a local superantigen response in which clonal T-cell activation and massive cytokine release occur in the affected skin. Second, these exotoxins can act as traditional allergens, stimulating a typical immunoglobulin E (IgE) response in the serum, which has been correlated with disease severity. This study is designed to begin the assessment of the hypothesis that a similar mechanism takes place in CS/NP. Serum was drawn from patients with CS/NP undergoing endoscopic sinus surgery as well as 13 atopic and nonatopic control subjects without sinusitis. IgE levels to S. aureus exotoxins A (SEA), SE exotoxins B (SEB), and toxic shock syndrome toxin 1 were measured using enzyme-linked immunosorbent assay. Tissue eosinophilia and the presence of lymphocytes on hemotoxylin and eosin-stained sections of polyps were scored by a blinded pathologist and correlated to presence of toxin IgE in the serum. Staphylococcal exotoxin (SE)-specific IgE was found in the serum of 5/10 (50%) of the patients with CS/NP. In contrast, 0/13 control patients had IgE to the exotoxins (p = 0.031). Polyp eosinophil, lymphocyte, and mononuclear cell counts were compared in IgE exotoxin-positive and -negative subjects. A trend toward increased eosinophil counts in patients with SE IgE (SE IgE+) was present, but not statistically significant. These results indicate that a high percentage of CS/NP patients show a systemic IgE response to S. aureus exotoxins in comparison with controls without CS/NP. Although these results are consistent with the actions of Staphylococcus toxins in other diseases, additional work is necessary to establish a local superantigen response in the nasal mucosa of CS/NP patients.

Anti-inflammatory effects of LY294002, a PI3K inhibitor, in a mouse model of asthma

Rationale Phosphatidylinositol 3-OH inase (PI3K) signaling cascade plays a pivotal role in the activation of inflammatory cells. The purpose of this study was to investigate the effects of LY294002, a specific PI3K inhibitor, on airway inflammation in an in vivo mouse model of asthma. Methods Mice were actively sensitized by intraperitoneal injections of ovalbumin (OVA) and challenged by aerosolized OVA. Airway hyperresponsiveness was measured using a single-chamber whole-body plethysmograph, airway inflammation with influx of eosinophils was measured using differential cell counting and histological examination, and elevation in cytokine and chemokine levels in bronchoalveolar lavage (BAL) fluid was determined using ELISA. Results LY294002 (1.625, 3.25 and 7.5 mg/kg) given intratracheally significantly inhibited OVA-induced airway hyperresponsiveness to inhaled methacholine in a dose-dependent manner (p<0.05). LY294002 at 7.5 mg/kg also markedly (p<0.05) attenuated OVA-induced increase in eosinophil count in BAL fluid and pulmonary eosinophilia in H&E stained lung section, and elevation of IL-13 and eotaxin levels in BAL fluid. Conclusions These results implicate that inhibition of PI3K signaling cascade may have therapeutic potential for allergic airway inflammation.

Safety profile of tegaserod, a 5-HT4 receptor agonist, for the treatment of irritable bowel syndrome.

This article reviews the safety and tolerability profile of tegaserod, a novel selective partial agonist of the serotonin 5-HT(4) receptor. Tegaserod was recently approved for the treatment of women with irritable bowel syndrome (IBS) with constipation. Tegaserod exhibits rapid absorption from the small intestine, and is excreted unchanged in the faeces and as metabolites in the urine. Meal ingestion decreases its bioavailability. There is little effect of age or gender on pharmacokinetics, although plasma levels may be slightly higher in the elderly. Tegaserod has no effect on plasma levels of other drugs metabolised by cytochrome P450 enzyme systems. Gastrointestinal symptoms are the most common adverse effects of tegaserod therapy. In data pooled from phase III randomised controlled trials (RCTs) in IBS with constipation patients, diarrhoea was reported by 8.8% of patients treated with tegaserod 6mg twice daily versus 3.8% of patients receiving placebo. Similar rates have been observed in international post-US marketing RCTs. In most patients, tegaserod-induced diarrhoea was mild and transient. In RCTs, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of IBS patients discontinued tegaserod due to diarrhoea. Since its release, rare cases of more severe diarrhoea and ischaemic colitis have been reported. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea, and flatulence) has been similar among tegaserod-treated patients and placebo-treated patients. Pooled analysis of phase III RCTs and post-US marketing RCTs have not demonstrated significant differences between tegaserod-treated patients and placebo-treated patients in the incidence of abdominal-pelvic surgery. There is no convincing evidence that rebound gastrointestinal symptoms occur upon termination of tegaserod therapy. Pooled analysis of phase III RCTs demonstrated an increase in the incidence of headaches among tegaserod-treated patients (6mg twice daily) compared with placebo-treated patients (15% vs 12.3%, respectively, p < 0.05), although post-US marketing RCTs have not observed this increase. Other extra-gastrointestinal adverse events occur with similar frequency among tegaserod-treated patients and placebo-treated patients. Tegaserod-treated patients in RCTs have not demonstrated significant prolongation of the QTc interval or cardiac arrhythmias compared with placebo-treated patients. Supra-therapeutic doses in healthy volunteers did not effect electrocardiographic parameters. Laboratory parameters are mostly unaffected by tegaserod, although several individuals have exhibited increased eosinophil counts. In summary, tegaserod exhibits a favourable safety and tolerability profile in IBS patients based on data from clinical trials. Diarrhoea is the most common adverse event associated with tegaserod use. Continued post-US marketing surveillance will further define the safety and tolerability profile of tegaserod.

The usefulness of inflammatory markers in monitoring treatment responses in asthma

The usefulness of inflammatory markers in monitoring treatment responses in asthma

Eosinophilic Variant of Chronic Myeloid Leukemia with Vascular Complications

Eosinophilic variant of CML (eoCML) is a unique disease with a poor prognosis. Like the hypereosinophilic syndrome (HES), eoCML has no clinically identifiable reason for an increased eosinophil count in the peripheral blood. In contrast to HES, eoCML patients carry a distinct chromosomal abnormality. The bcr/abl fusion gene (Philadelphia chromosome) is the genetic basis of this clonal disease. Recently, eoCML has been separated from HES. Patients with eoCML frequently suffer organ damage including the heart and lungs. This damage is related to the release of eosinophilic granules in the blood, which results in fibrosis of the endothelial lining. We report a case of a peripheral vasculitis complicated by gangrene of the fingers in a patient with eoCML. Despite an almost complete response to CML treatment with Gleevac, combined with prednisone, aspirin and Coumadin the patient sustained irreversible damage to the vascular lining of the distal arteries of the upper extremities.

Mast cells and T cells in Kimura's disease express increased levels of interleukin-4, interleukin-5, eotaxin and RANTES.

Kimura's disease (KD) is a chronic inflammatory disorder characterized by tumours in the head and neck region, enlarged lymph nodes, increased eosinophil counts andhigh serum IgE. Mast cells are known to play a central role in IgE-mediated allergic diseases through the release of inflammatory mediators like IL-4, IL-5 and chemokines. We hypothesized that mast cells may play a role in the pathogenesis of KD by regulating eosinophilic infiltration and IgE synthesis. In order to investigate the role of mast cells in the pathogenesis of KD, we examined the expression of cytokines/chemokines in the lesions of KD. We examined the number of tryptase+ cells, EG2+ cells, CD3+ cells, IL-4+ cells, IL-5+ cells, eotaxin+ cells, RANTES+ cells and CCR3+ cells in five specimens of KD versus normal tissues by immunohistochemistry. The sources of IL-4, IL-5, eotaxin and RANTES and the expression of CCR3 were examined by immunostaining of serial sections with antibodies to IL-4, IL-5, eotaxin, RANTES and CCR3, and antibodies to tryptase, ECP (EG2) and CD3. Mast cells, activated eosinophils, T cells, IL-4+ cells, IL-5+ cells, eotaxin+ cells, RANTES+ cells and CCR3+ cells were all increased in the lesions of KD as compared with those in normal tissue. Mast cells and T cells were the major source of IL-4, whereas mast cells, T cells and activated eosinophils were the main source of IL-5. Mast cells, T cells and activated eosinophils were the main source of eotaxin and RANTES. The number of IL-4, IL-5, eotaxin and RANTES-expressing mast cells and T cells were increased in the lesions of KD. As mast cells are lesional resident cells, these cells may play an important role in the pathogenesis of KD by regulating IgE synthesis and orchestrating eosinophilic infiltration.

Eosinophilia in sick neonates.

Eosinophilia is common in the neonatal period. However, its causes, pathomechanism and clinical significance are still unknown. Previous reports have described that eosinophilia may be associated with numerous conditions (establishment of an anabolic state, drug reactions, response to foreign antigens, chronic lung disease, erythropoietin treatment and infections). The aim of this study was to evaluate the possible association of various conditions, especially infection, with eosinophilia and to clarify whether recognition of increase in eosinophil count is of any clinical significance in the management of a sick neonate. Fifty-six neonates with eosinophilia (absolute eosinophil count > 700/mm3) and 55 control neonates matched for gestational age, birth weight and hospitalization days were included in the study. A significant difference between the two groups was found only in blood transfusions, immuno-globulin treatment, specific antibiotic treatment and infectious disease. However, neonates who develop sepsis and are treated with antibiotics and immuno-globulin are more often transfused. It can thus be concluded that the main relationship observed is between eosinophilia and infection whereas the other associations are secondary. The relative risk factor for infection when the absolute eosinophil count is > 700/mm3, is 1.58, with a confidence interval 1.30-1.91. Eosinophilia seems to be a reliable indicator of sepsis while normal absolute eosinophil count does not exclude infection. Infection should be strongly considered in the evaluation of a sick neonate with eosinophilia.

Increased eosinophil activity in acute Plasmodium falciparum infection--association with cerebral malaria.

To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8-10.7 ng/ml)) than in SA (4.7 ng/ml (3.0-7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6-5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.

The Kinetics of Allergen-induced Eotaxin Level in Nasal Lavage Fluid

Eotaxin (CCL11) is a potent eosinophil chemoattractant belonging to the C-C chemokine. To evaluate the role of eotaxin in eosinophilic inflammation in nasal mucosa, we investigated the levels of eosinophil chemoattractants in nasal lavage fluids obtained after antigen challenge, compared with eosinophil counts and eosinophil protein X (EPX) levels. In subjects with allergic rhinitis, allergen challenge led to parallel increases in eosinophil counts, levels of EPX, and eotaxin concentrations in nasal lavage fluid. The levels of eotaxin in lavage samples showed strong correlation with lavage levels of eosinophil counts and EPX. Normal subjects had few, if any, eosinophils and EPX as well as the measured parameters in their nasal lavage fluids before and after antigen challenge. In our experiments of eosinophil endothelial transmigration (TEM) assay using the nasal microvascular endothelial cells, eotaxin showed the most potent effect among various eosinophil chemoattractants. In addition, treatment of eosinophils with anti-CCR-3 mAb significantly blocked eosinophil TEM induced by homogenate of nasal mucosa. These results indicate that eotaxin has an important role in eosinophil-dependent inflammation in nasal mucosa and suggest that blocking eotaxin or CCR-3 might be useful for new therapeutic tools of allergic rhinitis.

Involvement of Eosinophils in the Early-Phase Allergic Reaction in a Guinea Pig Rhinitis Model

Background: Eosinophils are found in the nasal lavage fluid (NLF) and nasal biopsies of patients with allergic rhinitis after a nasal antigen challenge, and associated not only with a late-phase allergic reaction (LPR) but also an early phase allergic reaction (EPR). Numerous studies have been carried out to clarify the participation of eosinophils in LPR or airway hyperresponsiveness. However, there has been no published report describing in detail the role of eosinophils during EPR. To better understand the involvement of eosinophils in EPR, we studied the effects of repeated antigen challenges on nasal airway responsiveness and eosinophilic inflammation in EPR using a guinea pig rhinitis model. Methods: Nasal airway responsiveness was measured as the nasal airway resistance (NAR) after nasal antigen provocation. Eosinophilic inflammation during EPR was assessed by nasal lavage and histopathological examination using two groups of animals: those in group 1 were subjected to a sensitization pretreatment only, and those in group 2 were subjected to a pretreatment of sensitization followed by repeated nasal challenges. Results: Repeated antigen challenges induced nasal hyperresponsiveness as indicated by a decrease in the antigen provocation dose and a significant increase in NAR. Furthermore, significant increases in eosinophil counts, eosinophil peroxidase (EPO) activity and protein content in NLF during EPR were observed following antigen provocation in group 2. There were significant correlations between the levels of these parameters, and albumin was the most prevalent of the proteins in NLF. Histopathological examination showed that the degree of eosinophil infiltration into the lamina propria of the nasal mucosa of the animals in group 2 was significantly and apparently higher than in group 1. Particularly, epithelial disruption and mucosal edema were significantly elevated after antigen provocation in group 2. Conclusions: These results suggest that chronic eosinophil accumulation is induced by repeated antigen challenges in the nasal tissue, and that once antigen provocation occurs, eosinophils in the tissue are activated and responsible for the amplification of EPR such as vascular permeability and mucosal edema.