The role of cortisol in the peripheral granulocyte response to insulin-induced hypoglycaemia in man.

Peripheral blood leukocyte counts and plasma hormonal changes in response to acute insulin-induced hypoglycaemia were examined in 16 patients undergoing assessment of pituitary function. Eight subjects had a normal cortisol secretory response (Group 1), and 8 patients had definite hypopituitarism in whom the cortisol responses were deficient or absent (Group 2). An equivalent degree of hypoglycaemia was achieved in both groups. In Group 1a biphasic rise in leukocyte count occurred following hypoglycaemia, with an early rise in lymphocytes at 15 minutes after the acute hypoglycaemic reaction, and a later rise in granulocytes. A similar rise in lymphocytes was observed in Group 2, but the rise in the granulocyte count was attenuated, increasing from a basal value of 3.6 +/- 0.6 x 10(9) cells/L to a peak of 7.4 +/- 1.1 x 10(9) cells/L, compared with a peak of 11.7 +/- 1.2 x 10(9) cells/L in Group 1 (P less than 0.05). The usual increment in plasma cortisol in response to hypoglycaemia occurred in Group 1, but plasma cortisol did not rise in Group 2. A correlation was observed between the magnitude of the granulocyte rise and the increment in plasma cortisol in individual subjects (r = 0.64, P less than 0.02). This suggests that the rise in peripheral granulocytes following insulin-induced hypoglycaemia in man is mediated by cortisol released from the adrenal gland, following activation of the hypothalamic-pituitary-adrenal axis.

The effect of cromolyn sodium and albuterol on early and late phase bronchoconstriction and airway leukocyte infiltration after allergen challenge of nonanesthetized guinea pigs.

We describe the effects of the antiallergic drug cromolyn sodium and the beta 2-selective adrenoceptor agonist albuterol against early and late phase changes in specific airways conductance (sGaw) and leukocyte infiltration into the airways after allergen challenge of nonanesthetized guinea pigs. Inhalation of ovalbumin by sensitized guinea pigs induced three phases of airways obstruction: an early asthmatic response (EAR) peaking at 2 h, a late response (LAR) peaking at 17 h, and a further late response (LLAR) being observed at 72 h. The LAR was accompanied by a 13-fold rise in neutrophils and a four-fold rise in eosinophils recovered by bronchoalveolar lavage (BAL) at 17 h. By 72 h, the BAL content of neutrophils had returned to near normal, whereas eosinophil numbers had risen to 6.7-fold above baseline. Inhalation of an aerosolized solution of cromolyn, 10 mg/ml, 15 min before challenge inhibited both the EAR and LAR and the influx of neutrophils into the airways at 17 h but had no effect on eosinophil accumulation. Inhalation of cromolyn at 6 h, i.e., after the completion of the EAR, inhibited the LAR, the LLAR, and the rise in eosinophils at 72 h but did not reduce the influx of neutrophils at 17 h. Administration of cromolyn at both 15 min before and 6 h after challenge inhibited all changes in sGaw and reduced the accumulation of neutrophils at 17 h and the influx of eosinophils at 72 h. In contrast, inhalation of albuterol, 0.1 mg/ml, 15 min before allergen provocation blocked the EAR and the rise in BAL neutrophils at 17 h but did not inhibit the LAR. Inhalation of albuterol at 6 h partially reversed the LAR but had no effect on either the LLAR or cellular changes. Given at both times, albuterol inhibited the EAR and neutrophil accumulation at 17 h and partially reversed the LAR but produced no other effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Retinal blood velocity in patients with leukocyte disorders.

The blue light entoptic phenomenon was used to measure retinal blood velocity in eight patients with chronic granulocytic leukemia, six patients with leukopenia, and matched control subjects. The retinal leukocyte velocity of the leukemic patients was 0.53 +/- 0.26 (mean +/- SD) mm/s, whereas that of the matched control subjects was 0.46 +/- 0.14 mm/s. There was no significant difference between these two groups (power: 96% for a difference of 0.2 mm/s and 66% for 0.1 mm/s). There was also no significant difference between the leukocyte velocities of the leukopenic patients and control subjects (0.47 +/- 0.19 mm/s and 0.55 +/- 0.14 mm/s, respectively; 89% power for a difference of 0.2 mm/s, 59% for 0.1). There was a correlation between the leukocyte count and the number of leukocytes seen in the entoptoscope. The results suggest that retinal vascular autoregulation can compensate for changes in leukocyte numbers that might have been expected to alter retinal blood flow.

Leukocyte response in patients suffering from acute stroke.

The oxidation of adrenaline to adrenochrome has been shown to reflect the activation of leukocytes in vivo. We tested the in vivo activation of leukocytes by measuring plasma oxidation of adrenaline to adrenochrome in patients suffering from cerebral ischemia, cerebral hemorrhage, and transient ischemic attacks and in healthy subjects. Patients with cerebral ischemia and cerebral hemorrhage had significantly higher values than healthy subjects, while patients with transient ischemic attacks had values similar to those of healthy subjects. In some patients with cerebral ischemia, the test was repeated 4 and 15 days after the acute event, but the follow-up data did not differ from baseline values. Our study shows that leukocyte activation occurs in cerebral ischemia and cerebral hemorrhage.

Measurement of retinal blood flow in diabetes by the blue-light entoptic phenomenon.

Retinal blood flow velocity was measured in 24 normal volunteers and compared with the results obtained in 101 diabetics at different stages of retinopathy. The blue-light entoptic phenomenon was used to measure retinal flow velocity. Results showed that there was a significantly higher capillary flow velocity in those patients with background retinopathy (0.74 +/- 0.32 mms/s) over the group of normals (0.54 +/- 0.19 mm/s) and those diabetics with no retinopathy (0.51 +/- 0.24 mm/s). Retinal flow velocity was reduced at the preproliferative stage of retinopathy to 0.37 +/- 0.2 mm/s. Proliferative retinopathy showed a slightly greater flow velocity (0.56 +/- 0.27 mm/s), which was reduced following photocoagulation (0.42 +/- 0.14 mm/s).

Evidence in advanced cancer of an activated leukocyte state to explain the reversible defect in transmembrane signaling and leukocyte adherence inhibition to extracts of cancer.

When leukocytes bind tumor antigen, a transmembrane signal induces the cascade of physiological changes that result in leukocyte adherence inhibition (LAI). Leukocytes from patients with early stages of cancer exhibited transmembrane potential (delta psi) changes and LAI when incubated with a cancer extract of the same organ and histogenesis, whereas leukocytes from patients with advanced cancer did not. The refractoriness was reversed by transiently raising intracellular cyclic AMP. LAI is produced by leukotrienes and leukocytes from patients with advanced cancer were refractory to leukotriene-induced delta psi changes which was also restored by raising intracellular cyclic AMP. Moreover, leukocytes could be made refractory to delta psi changes: leukocytes from patients with early cancer when preincubated with a breast cancer extract showed no delta psi change with a second exposure; and leukocytes from control subjects preincubated with leukotrienes showed no delta psi change with a second exposure. The responsive population of leukocytes in LAI to either the specific cancer extract or leukotrienes consisted of about 35 to 42% of the adherent leukocytes. The responsive leukocytes in advanced cancer were already nonadherent, accounting for the 39% increased nonadherence with the control extract. Raising cyclic AMP decreased nonadherence by 39%. The results suggest that leukotrienes and other chemoattractants released in vivo by immune cells binding tumor antigen have stimulated the changes in leukocytes in advanced cancer. However, the unresponsiveness seems to be because of appropriate expression of physiological changes triggered by antigen and chemoattractant stimuli.

Cerebrospinal fluid shunts interfere with host defenses.

Despite advances in neurosurgical therapeutics, cerebrospinal fluid shunt infections have continued to complicate the management of patients with shunted hydrocephalus. Although various factors have been proposed to explain the pathogenesis of these infections, they have remained poorly understood. This in vitro study determined the ability of human neutrophils and monocytes to adhere to two types of shunt catheters and to phagocytose bacteria. These white blood cells failed to adhere in normal numbers to the catheters and failed to ingest fully a bacterial inoculum on the catheters' surfaces. While in contact with the shunt apparatus, the neutrophils also exocytosed myeloperoxidase, a major component of the intracellular microbicidal system. These observations suggest that the shunt apparatus may diminish the effectiveness of the hosts' defenses at the site of implantation.

Gonococcal infection in endotoxin-resistant and endotoxin-susceptible mice.

The role of endotoxin responsiveness in defense against gonococcal infection was studied in endotoxin-resistant (C3H/HeJ) and endotoxin-susceptible (C3H/HeN) mice by using a model of disseminated gonococcal infection (DGI) and a model of gonococcal survival in the female genital tract to determine the ability of the mice to eliminate gonococci. The 50% lethal dose in the DGI model was 10(9.6) for C3H/HeJ mice and 10(5.2) for C3H/HeN mice. Levels of bacteremia during infection indicated the C3H/HeJ mice cleared large numbers of gonococci from their peripheral blood by 24 h post-inoculation but that C3H/HeN mice did not. Additionally, the peritoneal leukocyte response after intraperitoneal inoculation of gonococci was greater in C3H/HeJ mice than in C3H/HeN mice, which suggested that the ability to mount an inflammatory response to endotoxin may be important in defense against DGI. Besides being different in susceptibility to DGI, C3H/HeJ mice were found to be more resistant then C3H/HeN mice to genital colonization by gonococci. The resistance of C3H/HeJ mice to genital colonization by gonococci appeared to be due to both the high numbers of polymorphonuclear leukocytes in the genital secretion and the predominance of inhibitory gram-negative genital flora in that mouse strain.