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Role of antibody to leukocytosis-promoting factor hemagglutinin and to filamentous hemagglutinin in immunity to pertussis.

Gamma globulins were obtained from rabbits hyperimmunized with the filamentous hemagglutinin (FHA) or the leukocytosis-promoting factor hemagglutinin (LPF.HA) of Bordetella pertussis. Double immunodiffusion analyses showed the antibodies to be highly specific for the homologous antigen. Intraperitoneal injection of anti-FHA or anti-LPF.HA into 10-day-old ICR mice 30 min before aerosol challenge with B. pertussis protected the mice from disease as evidenced by survival and a normal rate of gain in body weight. Both anti-LPF.HA and anti-FHA enhanced the clearance of B. pertussis from the lung and prevented leukocytosis which normally occurs after aerosol infection of mice with B. pertussis. Anti-LPF.HA, but not anti-FHA, neutralized the leukocytosis-promoting and histamine-sensitizing activities of LPF.HA when incubated with the purified protein in vitro. Anti-FHA, but not anti-LPF.HA, prevented the attachment of B. pertussis to mammalian cells (HeLa and Vero) in culture.

Animals↗

Effect of marked peripheral leukocytosis on the leukocyte count in ascites.

Patients with high peripheral leukocyte counts are sometimes found to have high leukocyte counts in ascitic fluid in the presence of negative cultures. To determine if peripheral leukocytosis (greater than or equal to 20 x 10(9)/L) by itself can result in high leukocyte or neutrophil counts in ascites, 29 patients were studied. A total of 31 paracenteses were performed in these patients as soon as the high peripheral leukocyte count was determined. Culture of ascitic fluid was performed using blood-culture bottles. The mean peripheral leukocyte count was 29.3 +/- 9.3 x 10(9)/L, with a mean neutrophil count of 19.9 +/- 6.5 x 10(9)/L. The mean ascitic fluid neutrophil count was 0.064 +/- 0.054 x 10(9)/L (range, 0.007 to 0.197 x 10(9)/L). No significant correlation was found between peripheral neutrophil (or leukocyte) count and neutrophil (or leukocyte) count in ascitic fluid. Marked peripheral leukocytosis (or neutrophilia) does not seem to have an effect on the leukocyte or neutrophil count in ascitic fluid.

Ascites↗

Spurious leukocytosis and thrombocytopenia. A dual phenomenon caused by clumping of platelets in vitro.

Three patients with spurious thrombocytopenia caused by in vitro clumping of platelets also had leukocytosis that was inappropriate for their clinical state and could not be verified on examination of a blood smear. Serial blood counts and analysis of the platelet and WBC histograms proved the "leukocytosis" to be spurious and caused by platelet clumps erroneously "recognized" by the counter as white blood cells. In three additional patients, the WBC counts increased concomitantly with a decrease in their platelet counts but remained within the normal range. Abnormal platelet and WBC counts generated by automated cell counters must be verified by examination of a blood smear before patients are subjected to unwarranted investigations and therapy.

Adult↗

Normal arterial oxygen saturation with the ear oximeter in patients with leukemia and leukocytosis.

Leukemic patients with severe leukocytosis experience a spurious lowering of the arterial oxygen tension if the arterial blood samples are not immediately analyzed. Arterial oxygen tensions were measured in three patients with acute leukemia; actual oxygen saturation was simultaneously measured with an ear oximeter. Blood gases demonstrated significant arterial hypoxemia even with immediate blood gas analysis in all patients. The ear oximeter in two patients revealed a relatively normal oxygen saturation while there was a simultaneous decrease in the calculated oxygen saturation. With reduction of the leukocyte count following chemotherapy in one patient, the calculated arterial oxygen saturation and the ear oximetry reading approximated one another. The ear oximeter is of value in the assessment of the true oxygenation status of patients who have leukemia and severe leukocytosis.

Adult↗

Leukocytosis due to adrenal metastases from malignant melanoma: reversal after bilateral adrenalectomy with long-term survival.

Leukocytosis has been noted in association with many non-hematologic malignancies in the absence of concurrent infection or metastatic involvement of bone marrow. We report a case of sustained, neutrophilic leukocytosis in a patient with disseminated malignant melanoma which reversed after bilateral adrenalectomy for adrenal metastases.

Adrenal Gland Neoplasms↗

Phenylhydrazine-induced leukocytosis in the rat.

Rats were injected with phenylhydrazine (PHZ) for periods of up to 6 months, during which time a marked leukocytosis was induced. The highest leukocyte counts occurred within 4-5 days following injection. An initial injection of 4 mg/100 gm body weight evoked a mean total leukocyte count of 129 X 10(3) cells/microliter. Successive weekly injections of 2 mg/100 gm resulted in a mean total leukocyte count of 70 X 10(3) cells/microliter compared to a mean total leukocyte count of 12.5 X 10(3) cells/microliter in saline-injected rats. Lymphocytes and monocytes accounted for approximately 75% of the total cell counts in both the PHZ-treated and control rats. The presence of increased numbers of mononuclear cells was confirmed by Percoll gradient separation and by phase-contrast microscopy. Although a leukocytosis was evident when using the automated Coulter electronic cell counter, it was not discernible when blood samples were counted manually in a hemocytometer by light microscopy. Histological examination of the thymus, lymph nodes, and spleen of the PHZ-treated rats indicated that lymphocytes and monocytes were mobilized from these sites. Lymphocyte depletion was evident, and germinal centers were found in all these lymphoid organs, indicating that PHZ induced a lymphopoietic response. A possible autoimmune etiology for PHZ-induced red blood cell destruction is discussed.

Animals↗

Prolonged effect of leukocytosis on reperfusion injury of rat intestine: real-time ATP change studied using (31)P MRS.

BACKGROUND: The intestine is one of the most sensitive tissues to ischemia and reperfusion (I/R). Polymorphonuclear neutrophils (PMN) may play an important role in ischemic injury. (31)P magnetic resonance spectroscopy (MRS) has been used to continuously monitor the energy metabolism of an animal in situ. We have applied MRS to study the effect of PMN on the I/R injury of rat intestine. MATERIAL AND METHODS: In a rat model of 30 min of intestinal ischemia and reperfusion, the number of PMNs was manipulated: group A, control; group B, leukopenia induced by cyclophosphamide; group C, leukocytosis induced by granulocyte colony-stimulating factor (G-CSF). MRS was employed to measure the level of real-time intestinal ATP and pH in vivo. RESULTS: In group A, ATP rapidly recovered on reperfusion to 61.0 +/- 11.0% of the preischemia level and maintained that level during reperfusion. The other two groups showed similar recovery of ATP at the initial phase of the reperfusion (<10 min). ATP in group B continued to recover, reaching 74.0 +/- 10.0% of the preischemia level. After the initial recovery, ATP in group C deteriorated reaching 46.0 +/- 4.4% of the preischemic level at 150 min of reperfusion. In group A and group B tissue pH decreased on ischemia and recovered on reperfusion in a similar manner. In group C, tissue pH was significantly lower than in other groups during I/R. CONCLUSION: Leukocytosis induced by G-CSF exerts a prolonged effect on ATP during I/R and leukocyte depletion helps protect against the I/R injury.

Adenosine Triphosphate↗

Lead-induced leukocytosis in female mice.

Lead acetate was shown to stimulate a striking leukocytosis in young adult female mice. The effect was manifest 4 days after lead injection and continued throughout the following 4 days. At the higher treatment level, lead induced an increase of 300% for both monocytes and neutrophils. The leukocytosis was due primarily to the elevated levels of neutrophils as suggested by a decrease in the ratios of peripheral agranulocytes to granulocytes. No differences from normal leukocyte cytology were observed in blood samples collected from animals receiving lead.

Animals↗

Leukocyte response to somatostatin in normals and patients with bacterial leukocytosis.

In normals and patients with acute bakterial leukocytosis synthetic somatostatin decreases cell count of stab neutrophils, neutrophils and eosinophils. After termination of somatostatin infusion a rebound phenomenon occurred. In healthy normals lymphocyte count increased during somatostatin infusion. This effect outlasts the end of infusion for more than 24 h. No significant effect could be demonstrated in patients with a bacterial leukocytosis.

Adult↗

Fecal leukocytosis, indium-111-labelled autologous polymorphonuclear leukocyte abdominal scanning, and quantitative fecal indium-111 excretion in acute gastroenteritis and enteropathogen carriage.

Abdominal scintiscans were performed and three-day fecal indium-111 radioactivity measured, following injection of indium-111-labeled polymorphonuclear leukocytes, in patients with acute gastroenteritis, enteropathogen carriage, exacerbations of chronic inflammatory bowel disease, and patients without gastrointestinal symptoms. The colon was more commonly inflamed than the small intestine in acute gastroenteritis. Fecal indium-111 radioactivity excretion was elevated in gastroenteritis and in chronic inflammatory bowel disease. The magnitude of the intestinal inflammatory response, as measured by fecal indium-111 excretion, is equivalent in acute gastroenteritis caused by a defined enteropathogen and exacerbations of chronic inflammatory bowel disease. All patients with microscopically detected fecal leukocytosis gave positive intestinal scintiscans, whereas negative scans were obtained on patients without fecal leukocytosis. The results of this study suggest that indium-111-labeled polymorphonuclear leukocytes can be used to study pathophysiology of the enteric inflammatory response in acute infectious gastroenteritis.

Adult↗

Pertussis with severe pulmonary hypertension and leukocytosis treated with extracorporeal membrane oxygenation.

Pertussis, or "whooping cough," is a highly communicable disease caused by the coccobacillus Bordetella pertussis. Pertussis remains one of the most common causes of death from infectious diseases worldwide. We describe a 5-week-old infant girl who presented with severe pertussis infection associated with extreme leukocytosis and required prolonged extracorporeal membrane oxygenation (ECMO). Nitric oxide therapy resolved the pulmonary hypertension, and she was successfully weaned from ECMO and discharged home after 3 months. We report successful application of ECMO for severe pertussis-induced respiratory failure despite multiple grave prognostic indicators (<1 year age, leukocytosis, pulmonary hypertension) and discuss the role of extracorporeal life support in treating pertussis.

Extracorporeal Membrane Oxygenation↗

Methylprednisolone-induced neutrophil leukocytosis--down-modulation of neutrophil L-selectin and Mac-1 expression and induction of granulocyte-colony stimulating factor.

The mechanisms underlying corticosteroid-induced neutrophil leukocytosis are not fully understood; however, leukocyte/endothelial cell adhesion molecule interactions are known to be key to the movement of neutrophils within and out of the vasculature. This study was designed to investigate the effects of corticosteroids on neutrophil adhesion molecules in relation to neutrophil leukocytosis. Circulating neutrophil counts, neutrophil L-selectin and Mac-1 expression (measured by flow cytometry), soluble L-selectin, and granulocyte-colony stimulating factor concentrations were determined in 15 multiple sclerosis patients receiving intravenous methylprednisolone prior to and at 6 and 24 h following the initial 500-mg dose. A follow-up sample was obtained 48 h after the 5-day therapeutic course. Neutrophil counts were elevated at 6 h (threefold) and 24 h (twofold). This was associated with a 40% reduction in L-selectin expression at 6 and 24 h and a 35% reduction in Mac-1 expression at 6 h. Serum granulocyte-colony stimulating factor levels were increased (6 h: threefold; 24 h: twofold), whereas soluble L-selectin concentrations were unaltered. All of the above parameters had returned to basal levels in the follow-up sample. Short-term in vitro cultures (6 and 24 h) of blood samples from untreated multiple sclerosis patients and controls with 0.01 mg/ml methylprednisolone resulted in minimal reductions in neutrophil L-selectin and Mac-1 and no change in soluble L-selectin. Granulocyte-colony stimulating factor induced Mac-1 expression in a dose-dependent manner, whereas L-selectin expression was unaffected or reduced at high concentrations. Reduction in neutrophil L-selectin and Mac-1 expression following methylprednisolone infusion may cause decreased adhesion of marginated neutrophils and/or reduced capacity of neutrophils to migrate from the vasculature. Additionally, the induction of granulocyte-colony stimulating factor may contribute to neutrophil production and release into the circulation.

Down-Regulation↗

Leukocytosis and left shift associated with quinidine fever.

Fever is a well-known side effect of quinidine therapy, but an elevated white blood cell count is considered unusual. Two patients are described who had leukocytosis or a marked left shift in the white blood cell count (or both) in association with quinidine fever. Neither patient had evidence of infection. In each of these patients, the temperature and white blood cell count returned to normal within two days after quinidine was discontinued. Although infection should always be considered in a patient with fever, leukocytosis, and a left shift, these may also appear in association with quinidine therapy.

Aged↗

Determination of leukocytosis in traumatic spinal tap specimens.

White and red blood cell counts from peripheral blood and from the cerebrospinal fluid of all patients who had traumatic lumbar punctures over a five-year period were studied to determine the diagnostic value of using the ratio of white blood cells to red blood cells in peripheral blood to adjust the white blood cell count found in the bloody cerebro-spinal fluid. In patients without meningitis, 55 percent of the cerebrospinal fluid specimens had more white blood cells than could be attributed to trauma. However, in only 10 percent was the actual white blood cell count more than 10 times greater than the number referable to trauma. In 38 percent, there were fewer white blood cells in the cerebrospinal fluid than the ratio predicted. Such underestimation was uncommon among patients with culture-positive meningitis: the ratio failed to detect leukocytosis in only 10 percent, and all but one of these patients had clinical reasons for the low cerebrospinal fluid count. It is concluded that true leukocytosis is rarely masked in blood-contaminated cerebrospinal fluid, and that the presence of more than 10 times the number of white blood cells than allowed by the adjustment is a sensitive and specific indicator of meningitis. However, a simple mechanical use of the formula is not justified, and all available clinical and laboratory data should be used when deciding whether to institute treatment in a patient with possible meningitis and bloody spinal fluid.

Adult↗

The thromboxane receptor antagonist, daltroban, protects the myocardium from ischaemic injury resulting in suppression of leukocytosis.

The cardioprotective action of the new selective inhibitor of thromboxane receptors, daltroban (BM 13.505), was studied in cats subjected to 3 h of coronary artery ligation followed by 2 h of reperfusion. In comparison with vehicle (physiological saline)-treated cats, daltroban (20 mg/kg per h i.v.) reduced the ischaemia-induced rise in the ST segment and prevented the development of a Q-wave in the ECG during reperfusion. This was paralleled by a significantly improved preservation of creatine-phosphokinase activity in the ischaemic myocardium. Daltroban significantly attenuated platelet ATP secretion, the U-46.619-induced contraction of the cat thoracic aorta ex vivo and the myeloperoxidase-associated generation of reactive oxygen species ex vivo. These effects could be largely attributed to the inhibition of ischaemia-induced leukocytosis. It is concluded that daltroban protects the myocardium from ischaemic injury and that this effect involves prevention of ischaemia-induced leukocytosis.

Adenosine Triphosphate↗

Inhibition of interleukin 1 (IL-1)-elicited leukocytosis and LPS-induced fever by soluble immune response suppressor (SIRS).

IL-1-induced leukocytosis was inhibited or blocked in a dose-dependent manner by SIRS, an antigen-nonspecific suppressive lymphokine, when administered intravenously or per os to CBA mice. Timing experiments showed that SIRS effectively inhibited the leukocytosis when administered within 30 minutes of the IL-1. An antipyrogenic activity of SIRS was observed in rabbits injected intravenously with LPS. SIRS, given intravenously in one or two doses, markedly reduced LPS-induced fever. SIRS (2000 units) was a more effective antipyretic agent than aspirin (3 mg/kg body weight, intramuscularly). The results suggest that SIRS may be a potential drug for use in IL-1-mediated disorders.

Animals↗

Early age onset of hairy cell leukemia presenting with leukocytosis.

Hairy cell leukemia (HCL) is an uncommon type of chronic B cell leukemia mainly affecting middle-aged adults. HCL presenting with pancytopenia is rare in Japan and a distinct subtype of HCL termed HCL-Japanese variant is predominantly seen. We describe a HCL patient with unusual presentation. The patient was a 26-year-old male, such early onset of HCL being quite rare. The patient showed leukocytosis with many circulating hairy cells and cellular bone marrow. These findings were preferentially seen in HCL-Japanese variant, but, cytomorphologic, cytochemical and immunophenotypical studies on the pathologic cells were consistent with those of typical HCL seen in Western countries. Interferon-alpha therapy was very effective in this case. Differentiation of the subtype of HCL appears to be important for the choice of the treatment. The cytological findings were useful for the differential diagnosis of HCL presenting with leukocytosis.

Acid Phosphatase↗

A case of squamous cell carcinoma of the head and neck producing granulocyte-colony stimulating factor with marked leukocytosis.

In squamous cell carcinoma of the head and neck (SCCHN), tumor cells have been shown to secrete detectable amounts of various cytokines, such as interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta. These tumor-derived factors might be responsible for promoting malignancy. Here, we describe a SCCHN patient with tumor produced G-CSF and characterized by marked leukocytosis. In this 45-year-old man, severe leukocytosis developed in parallel with aggressive tumor growth. G-CSF production by the tumor was confirmed by immunohistochemistry (IHC). Serum G-CSF levels were elevated. The leukocyte counts and the blood G-CSF level decreased following a course of radiotherapy. Tumor cells were also positive for G-CSF receptor, suggesting autocrine growth regulation by G-CSF. Moreover, the tumor cells were also investigated by IHC with anti-p53, anti-P-glycoprotein (P-gp), anti-thymidylate synthase (TS), and anti-dihydropyrimidine dehydrogenase (DPD), which molecules are thought to contribute the acquisition of therapeutic resistance. The tumor cells were positively stained for TS and DPD, but neither p53 nor P-gp. These results suggest that a variety of molecules may be responsible for acquisition of high malignancy.

Abscess↗