M. Klokker

The natural killer cell response to exercise in spinal cord injured individuals

Abstract In order to evaluate exercise-induced changes in natural killer (NK) and other immunocompetent cells in spinal cord injured individuals, immunological competent blood cells and stress hormones were followed in five paraplegic and six quadriplegic subjects in relation to 30 min electrically stimulated cycling exercise. The leukocyte and lymphocyte concentrations increased during exercise. In the recovery period, the concentration of neutrophils increased, whereas the lymphocytes decreased. The percentage and concentration of NK cells increased during exercise in the paraplegic group and returned to pre-exercise level 2 h after, whereas no changes were seen in these measures for the quadriplegic group. No changes in activated CD38+ NK cells appeared. Unstimulated and interferon-α or interleukin-2 stimulated NK cell activity increased during exercise and returned to pre-exercise level 2 h after with no distinction between paraplegics and quadriplegics. The concentrations of plasma growth hormone and catecholamines increased during exercise, with the rise in epinephrine being more pronounced in paraplegic than in quadriplegic subjects, indicating a difference between the groups in sympathetic nervous system integrity. The sympathoadrenal activity is concluded to be responsible for recruitment of NK cells to the blood during exercise.

Peripheral venous oxygen saturation during head-up tilt induced hypovolaemic shock in humans

We followed central, median cubital and dorsal metacarpal venous oxygen saturations (SvO2) during 50 degrees head-up tilt (anti-Trendelenburgs position) induced central hypovolaemia in eight males. Head-up tilt resulted in slight tachycardia of 101 (60-120) beats min-1 (median with range) and a stable mean arterial pressure (MAP) of 100 (88-114) mmHg. After 13 (6-23) min presyncopal symptoms appeared, accompanied by decreases in heart rate to 75 (51-97) beats min-1 and in MAP to 59 (49-76) mmHg (p < 0.01). Cardiac output decreased 0.9 (0.3-1.6) 1 min-1 while thoracic electrical impedance increased 3.4 (-1.2-5.9) Ohm (p < 0.01). Tilt-up decreased central venous pressure, but during sustained tilt it remained unchanged. Arterial oxygen saturation did not change. Head-up tilt decreased central SvO2 by 12 (5-24)% (p < 0.01). Median cubital SvO2 decreased 8 (-5-25)% (p < 0.02) during tilting, and it remained at this level during sustained tilt. Only five of eight samples from the dorsal metacarpal vein could be obtained. In these samples SvO2 was lowered by 15 (7-26)% (p = 0.01) at the onset of presyncopal symptoms. The results indicate that loss of central blood volume is reflected in central as well as peripheral SvO2. However, for reliable monitoring of blood volume changes, central SvO2 is the most useful variable, as this SvO2 changed consistently with the central blood volume, and blood samples could be obtained readily from the central venous catheter.

Effects of Isoprinosine Treatment of HIV‐Positive Patients on Blood Mononuclear Cell Subsets, NK‐ and T‐Cell Function, Tumour Necrosis Factor, and Interleukins 1, 2, and 6

The immunomodulatory drug isoprinosine has been found to delay the occurrence of opportunistic infections in HIV‐infected individuals. To elucidate the mechanism of action, eight HIV‐positive, healthy patients were treated with isoprinosine, 3 g/day for 28 days; six patients received no treatment but were examined in parallel, and two patients were withdrawn. All patients had blood collected just before the start as well as on days 14 and 28 of isoprinosine treatment.

Influence of Naloxone on the cellular immune response to head-up tilt in humans

Abstract To evaluate a possible role for β-endorphin in the stress-induced modulation of natural killer (NK) cells, immunologically competent blood cells were followed in eight male volunteers administered either Naloxone or saline (control) during head-up tilt maintained until the appearance of presyncopal symptoms (PS). The PS appeared more rapidly with Naloxone compared to control [5.7 (SEM 1.1) vs 22.3 (SEM 5.1) min; P = 0.01]. The NK cell activity increased threefold during PS partly due to an increase in CD16+ and CD56+ NK cells in blood. In support, NK cell activity boosted with interferon-α and interleukin 2 rose in parallel with unboosted NK cell activity and NK cell concentration and activities returned to the baseline level after 105 min. The total lymphocyte count and the concentrations of CD3+, CD4+, CD8+, CD16+, and CD56+ cells increased during PS. Head-up tilt also induced an increase in plasma adrenaline concentration during control PS and a rise in plasma cortisol and adrenocorticotropic hormone concentrations up to 30 min thereafter, whereas no significant changes were found in plasma concentrations of noradrenaline, growth hormone, or β-endorphin. The results would indicate an influence of endorphin on the increase in plasma adrenaline concentration during head-up tilt and at the same time contra-indicate a significant role for adrenaline in the provocation of PS. The influence of head-up tilt on plasma β-endorphin was too small to influence the modulation of the cellular immune system.

Effects of isoniazid treatment on human lymphocyte proliferative response, lymphocyte subsets and natural killer cell activity

The effect of isoniazid on proliferative response, natural killer (NK) cell activity and lymphocyte subset distribution of blood mononuclear cells (BMNC) was investigated. To evaluate the effect of treatment with isoniazid in pharmacologic concentrations, twenty healthy HIV-seronegative volunteers were randomized into two groups: one group received isoniazid tablets plus pyridoxin tablets once a day for 30 days, the other group received pyridoxin only. Blood samples were collected on day 0 and day 30. Inhibition of the PHA-induced proliferative response was demonstrated in lymphocyte cultures from isoniazid-treated volunteers (p < 0.001). However, no effect was seen on the IL-2- or antigen (PPD)-induced proliferative response or the NK cell activity of isolated BMNC. Inhibition of the PHA-induced proliferative response could not be related to changes in the distribution of CD3+, CD4+, CD8+, CD14, or CD19+ lymphocyte subsets. The effects, in vitro, were investigated by addition of isoniazid to cultures of BMNC isolated from either HIV-seroposive or HIV-seronegative donors who did not receive any treatment. We found that isoniazid did not influence the mitogen- or antigen-stimulated proliferative response or the NK cell activity.