| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
has immunomodulatory effects with minor
endocrine and metabolic effects in humans
1 Department of Endocrinology
and Metabolism and 2 Clinical and
Laboratory Immunology Unit, To evaluate
whether interferon-
cytokines; hormones; energy expenditure; metabolism; immune system; human leukocyte antigen-DR; neopterin
THERE IS INTENSIVE INTERACTION between the immune and
endocrine systems. This interaction involves both inhibitory and
stimulatory effects of hormones on the immune system and, conversely,
stimulatory and inhibitory effects of the immune system on the
endocrine system (7, 12, 18, 19, 35). Mediators like cytokines
participate in the interaction between these two systems (3, 5). In addition to effects on the immune system, tumor necrosis factor- IFN- To evaluate whether IFN- Subjects.
Six healthy men [age 22 ± 1 (SE) yr, weight 76.1 ± 3.5 kg, height 1.85 ± 0.03 m] participated in the
study. All were in good health, did not experience any febrile disease
in the month before the study, did not use any medication, and gave
written informed consent. The study was approved by the Research
Committee and the Medical Ethical Committee of the Academic Medical
Center, Amsterdam.
Study design (Fig. 1).
Each subject was studied twice, with an interval of at least 4 wk. On
one occasion the subjects received recombinant human (rh) IFN-
ABSTRACT
Top
Abstract
Introduction
Methods
Results
Discussion
References
(IFN-) is involved in the interaction between
the immune and endocrine systems in vivo, we studied six healthy
subjects twice in a placebo-controlled trial: once after administration
of recombinant human IFN- and, on another occasion, after
administration of saline. The rate of appearance of glucose was
determined by infusion of
[6,6-2H2]glucose
and resting energy expenditure by indirect calorimetry. Human leukocyte
antigen-DR gene expression on monocytes and serum neopterin increased after administration of IFN-
(P < 0.05 vs. control). IFN-
increased serum interleukin-6 levels significantly. Levels of tumor
necrosis factor-
remained below detection limits. IFN- increased
plasma concentrations of ACTH and cortisol
(P < 0.05 vs. control), IFN- did
not alter concentrations of growth hormone,
(nor)epinephrine, insulin, C peptide, glucagon, or insulin-like growth
factor I. IFN- did not alter plasma concentrations of glucose and
free fatty acids nor the rate of appearance of glucose. IFN-
increased resting energy expenditure significantly. We conclude that
IFN- is a minor stimulator of the endocrine and metabolic pathways.
Therefore, IFN- by itself is probably not a major mediator in the
interaction between the immune and the endocrine and metabolic systems.
INTRODUCTION
Top
Abstract
Introduction
Methods
Results
Discussion
References
(TNF-), interleukin-2 (IL-2), interferon- (IFN-), and IL-6 induce in humans profound endocrine and metabolic effects (4, 6, 25,
26, 30). Remarkably, despite more or less similar endocrine effects,
the metabolic effects are different between the different cytokines.
For instance, we and others observed that TNF-, IFN-, and IL-6
all increased lipolysis to a variable extent (6, 25, 26, 30), whereas
IL-2 inhibited lipolysis (4). The effect on glucose metabolism was also
contradictory between the different cytokines, despite comparable
changes in plasma concentrations of glucoregulatory hormones.
is a cytokine involved in different diseases such as viral
infections and sepsis (20, 32). However, the endocrine and metabolic
effects of IFN- in humans in vivo have not been studied in any
detail. Therefore, it is unclear whether IFN- is another cytokine
involved in the interaction between the immune and endocrine systems.
, besides immunomodulatory effects, also
induces endocrine and metabolic effects, we studied the immunologic,
endocrine, and metabolic effects of IFN- administration in healthy
volunteers in a saline-controlled crossover study.
METHODS
Top
Abstract
Introduction
Methods
Results
Discussion
References
, on
the other occasion saline (control study). The order in which rhIFN-
or saline was given was determined by balanced assignment. All
volunteers consumed a weight-maintainance diet, containing at least 250 g of carbohydrates. The subjects fasted from 6:00 PM the day before the
study until the end of the study. At 6:45 AM, a catheter was placed
into an antecubital vein for infusion of stable isotope tracers.
Another catheter was inserted retrogradely into a contralateral vein of
a hand the subject inserted and kept within a thermoregulated
(65°C) Plexiglas box for sampling of arterialized venous
blood. The catheters were kept patent by infusion of
0.65% NaCl (30 ml/h). During both studies the subjects were confined
to bed. At 7:00 AM (t = 
2 h)
blood was sampled for determination of background enrichment, and a
primed (17.6 µmol/kg), continuous (0.22 µmol · kg
1 · min1)
infusion of
[6,6-2H2]glucose
(Isotec, Miamisburg, OH) was started and continued until the end of
each study (t = 12 h). At
t = 15, 10, 5,
and 0 min, blood samples for determination of isotope enrichment of glucose were drawn. Blood samples for baseline values of hormones, substrates, cytokines, and human leukocyte antigen (HLA)-DR gene expression on monocytes were drawn just before
t = 0 min. At
t = 0 min, rhIFN- (100 µg/m2, Immukine, Boehringer
Ingelheim, Ingelheim/Rhein, Germany) or the same volume of saline was
injected subcutanously. At 1, 2, 4, 6, 8, 10, and 12 h after injection
of rhIFN- or saline, blood was drawn for the measurement of isotope
enrichment, hormone, substrate, and cytokine concentrations.
Twenty-four hours after the injection of rhIFN- or saline, blood was
drawn for determination of cytokine and neopterin serum levels. Blood
samples taken at 4, 8, and 24 h after administration of rhIFN- were
also analyzed for HLA-DR expression on monocytes. Blood pressure (Riva
Rocci method, brachial artery), pulse rate (palpation of radial
artery), and oral temperature (Terumo digital clinical thermometer C11, Terumo, Tokyo, Japan) were recorded hourly. Oxygen consumption and
carbon dioxide production were determined every 2 h by indirect calorimetry, using the method of a ventilated hood (model 2900, computerized energy-measurement system, Sensor Medics, Anaheim, CA).
View larger version (10K):
[in a new window]
Fig. 1.
Study design. All subjects were studied twice, once after
administration of recombinant human (rh) interferon (IFN)- and, on
another occasion, after administration of saline. RQ, indirect
calorimetry.
Assays. All measurements in each individual subject were performed in the same run, with the exception of flow cytometry analysis. All samples were tested in duplicate.
Glucose concentration and enrichment were determined according to Reinauer et al. (21), using phenyl-
-D-glucoside as an internal standard. The gas chromatography column used was a Heliflex AT-1 capillary column [30 m × 0.25 mm, film
thickness (df) 0.2 µm)] (Alltech, Deerfield, IL) on an HP 5890 series II gas chromatograph coupled to an HP 5989 A mass spectrometer
(Hewlett-Packard, Palo Alto, CA). Mass spectra were recorded at
mass-to-charge ratio (m/z)
187 for glucose and
m/z
189 for
[6,6-2H2]glucose.
The internal standard was monitored at
m/z
127 and 169.
Free fatty acids were determined by using the NEFA C kit (code no.
994-75409 E) from Wako Chemicals (Neuss, Germany).
Plasma insulin concentration was measured by RIA [insulin RIA
100, Pharmacia Diagnostic, Uppsala, Sweden; intra-assay coefficient of
variation (CV) 3-5%, interassay CV 6-9%], and C
peptide was measured by RIA (RIA-coat c-peptid, Byk-Sangtec
Diagnostica, Dietzenbach, Germany; intra-assay CV 4-6%,
interassay CV 6-8%). Glucagon was determined by RIA (Linco
Research, St. Charles, MO; detection limit 15 ng/l, intra-assay CV
3-5%, interassay CV 9-13%), insulin-like growth factor I by
immunoradiometric assay after a modified acid-ethanol extraction procedure (DSL, Webster, TX; detection limit 5 nmol/l, intra-assay CV 2-4%, interassay CV 3-8%). Cortisol was
measured by using a fluorescence polarization immunoassay (Abbott
Laboratories, North Chicago, IL, intra-assay CV 6.4%, interassay CV
9.0%), ACTH by immunoluminometric assay (Nichols Institute, Los
Angeles, CA; intra- and interassay CV 4.3 and 5.4%, respectively), and
growth hormone by immunoluminometric assay (Nichols Institute;
detection limit 1 mU/l, intra- and interassay CV 7.3 and 9.6%,
respectively). Catecholamines were measured by an in-house HPLC method.
Essentially, norepinephrine (inter- and intra-assay CV 13 and 6%,
respectively) and epinephrine (inter- and intra-assay CV 14 and 7%,
respectively) were selectively isolated by liquid-liquid extraction and
derivatized to fluorescent components with 1,2-diphenylethylenediamine.
The fluorescent derivatives were separated by reverse-phase liquid chromatography and detected by fluorescence detection (23, 29).
IL-6 and TNF- were determined by an ELISA (CLB, Amsterdam, The
Netherlands), both with a detection limit of 2 pg/ml. IFN- was
measured by using an ELISA with a detection limit of 31 pg/ml (16).
Serum concentrations of neopterin were measured by RIA (IMMUtest
Neopterin, Hennig, Berlin, Germany).
HLA-DR expression was measured by using flow cytometry. Whole blood was
lysed twice, using ammonium chloride (0.155 M) with K-EDTA, and was
subsequently washed with PBS supplemented with bovine serum albumin
(0.5% wt/vol), sodium azide (0.01% wt/vol), and potassium EDTA (0.5 mM; PBAP). Before and after these lysis steps, cells were fixed with
paraformaldehyde, 0.5 and 2% wt/vol, respectively. Subsequently, Fc
receptors were blocked by using human pooled serum (10% vol/vol) in
PBAP. Then, cells were incubated with anti-HLA-DR monoclonal antibodies
directly labeled with FITC (Becton-Dickinson, San Jose, CA). Irrelevant
mouse monoclonal antibodies directly labeled with FITC were used as the
control for background staining. After 30 min, the incubated cells were washed and suspended in PBAP. Cells were kept on ice during incubation periods. For washing procedures, cold media were used. Data acquisition was performed on a FACScan flow cytometer (Becton-Dickinson). All data
were saved. Analysis was stopped after 5,000 counts in the lymphogate
had been measured. Monocytes were gated by forward- and side-scatter parameters.
Calculations and statistics.
All data are presented as means ± SE. After administration of
IFN-, the rate of appearance
(Ra) of glucose was calculated by using Steele's equation for non-steady-state conditions adapted for
stable isotopes (21). The data were analyzed by analysis of variance
for randomized block design and the Wilcoxon test to compare data at
individual time points. P < 0.05 was
considered to represent statistical significance.
| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Clinical effects of IFN- (Fig.
2).
IFN- caused an increase in temperature from 36.2 ± 0.2 to 36.9 ± 0.1°C (P < 0.05 vs.
control study) (Fig. 2). Blood pressure was not different between the
control and intervention studies, whereas the pulse rate increased
after IFN- (from 59 ± 3 to 72 ± 3 beats/min)
(P < 0.05 vs. control study) (Fig.
2).
|
IFN- plasma concentration (Fig.
3).
During the control study, IFN- levels remained below or just above
the detection limit of the assay (31 pg/ml). In the intervention study,
IFN- levels increased gradually to 518 ± 96 pg/ml after 6 h
(P < 0.05 intervention vs. control)
(Fig. 3). The plasma values of IFN- 24 h after IFN- injection
were not different from pretreatment values.
|
Effects of IFN- on plasma cytokine concentrations.
IFN- induced a modest but significant rise in IL-6 levels, with a
peak after 12 h [2 ± 1 (control) vs. 5 ± 1 pg/ml (IFN- study) (P < 0.05)]. On the
other hand, TNF- levels were always below the detection limit of our
assay (2 pg/ml).
Effects of IFN- on HLA-DR expression on monocytes
and monocyte activation (Fig. 3).
IFN- induced a considerable change in HLA-DR expression on
monocytes. After an initial decrease, mean fluorescence intensity of
HLA-DR on monocytes increased from 84 ± 7 to 181 ± 34 arbitrary units at t = 24 h after
IFN- administration (P < 0.05 vs.
t = 0 h). No significant changes were
observed in the control study. Serum neopterin levels increased almost
threefold after the administration of IFN- from 4.7 ± 0.7 to 11.92 ± 0.94 nmol/l after 24 h
(P < 0.05 vs.
t = 0 h).
Endocrine effects of IFN- (Fig.
4).
Baseline hormone levels did not differ between the two studies. After
administration of IFN-, there was a modest, transient increase in
ACTH and cortisol levels with a peak after 4 h
(P < 0.05 vs. control) (Fig. 4).
Insulin and C peptide gradually decreased in time during both studies
(P < 0.05 vs.
t = 0 h), but no difference between
the two study periods could be detected (Fig. 5). There were no
differences between the two studies in growth hormone, glucagon,
epinephrine, and norepinephrine levels (Figs. 4 and
5). insulin-like growth factor I
concentrations decreased significantly in time during both studies, but
no IFN- effect was measurable in the intervention study.
|
|
Effects of IFN- on substrates and energy metabolism
(Fig. 5).
Baseline values did not differ between both study periods. Plasma
glucose concentrations and Ra
glucose decreased during the control study
(P < 0.05 vs.
t = 0 h). There was no effect of
IFN- on plasma glucose concentration or
Ra glucose (Fig. 5). Plasma free
fatty acid concentrations increased during the control study from 0.52 ± 0.08 (baseline) to 0.97 ± 0.20 mmol/l
(t = 12 h,
P < 0.05) (Fig. 5). There was no
effect of IFN- on free fatty acid concentrations (Fig. 5).
increased resting energy expenditure significantly at 6 h after
IFN- administration by ~11% compared with the control study
[1,867 ± 41 (control) vs. 2,064 ± 45 kcal/day (IFN-
study) (P < 0.05)] (Fig.
5).
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
In this study, the endocrine, metabolic, and immunologic effects of
IFN- were evaluated in healthy humans. IFN- had
clear effects on HLA-DR expression on monocytes in
peripheral blood and on serum neopterin levels, both reflecting
activation of monocytes and macrophages (27). IFN- also induced a
slight but significant increase in serum IL-6. Despite these clear
effects of IFN- on the immune system, there were only minimal
effects on the endocrine and metabolic pathways. With the exception of
a short-lived stimulation of the pituitary-adrenal axis, there were no
endocrine effects of IFN- detectable. The metabolic effects of
IFN- were limited to a small stimulation of resting energy
expenditure by ~11% without any effect on glucose and fat
metabolism. Therefore, we conclude that IFN- is not a major mediator
between the immune and endocrine systems.
Clinically irrelevant plasma concentrations of IFN-
are not the explanation for the limited endocrine and metabolic effects observed in our study. The dose of IFN- in our study resulted in
plasma levels of IFN- that are well within the range of those reported in several diseases. In acute falciparum malaria, IFN- levels were 123 ± 71 pg/ml, 215-396 pg/ml in human
immunodeficiency virus infection, and 238-867 pg/ml in pneumonia
(15, 22, 33, 34). However, we cannot exclude that a higher dose of
IFN- might have resulted in more pronounced endocrine and metabolic effects. Nonetheless, the purpose of our study was to evaluate pathophysiologically relevant, rather than pharmacological, effects of
IFN-. IFN- induced a marked increase in HLA-DR expression on
monocytes in peripheral blood and a rise in neopterin serum levels, in
accordance with previous in vivo and in vitro studies (1, 2, 14, 17,
27). Apparently, our IFN- levels were sufficient to induce
immunologic effects but not to induce metabolic and endocrine
alterations. It could be argued that a longer observation period could
have revealed distinct influences of IFN-. However, metabolic
alterations due to acute phase response-like reactions induced by
cytokines take place after a short-term interval. A cytokine-mediated
metabolic response after 12 h is not to be expected.
Our results are hard to compare with data from the literature because
the endocrine effects of IFN- are scarcely investigated in humans
and there are no data on metabolic effects. In accordance with our
results, IFN- increased plasma cortisol levels 2-6 h after
administration in two other studies in humans (8, 24). The data on ACTH
in human studies are contradictory. In accordance with our results,
Goldstein et al. (8) also observed an ACTH peak after IFN-, whereas
Holsboer et al. (9) did not find a ACTH peak despite an increase in
plasma cortisol. In our study and the study by Goldstein et al. the
cortisol peak coincided with the ACTH peak. These observations and
those of Holsboer et al. suggest that the increase in plasma cortisol
may not mainly be due to ACTH stimulation; it leaves open the
possibility of a direct stimulating effect of IFN- on the adrenal
gland. This assumption is supported by in vitro data (28). The effect
of IFN- on ACTH secretion has also been studied in vitro. In rat anterior pituitary cells, homologous IFN- did not affect basal ACTH
production but inhibited the stimulatory effect of
corticotropin-releasing hormone on ACTH production (31).
Therefore, it is unlikely that IFN- stimulates ACTH secretion
directly. Alternatively, other factors can be involved. For instance,
IFN- increased IL-6 production, which in turn stimulates ACTH
secretion (26).
In contrast to IFN-, cytokines like TNF-, IL-6, and IFN- have
major effects on endocrine and metabolic regulation in humans. Administration of TNF-, IL-6, or IFN- results in prolonged and massive stimulation of the pituitary-adrenal axis and secretion of
glucagon and catecholamines without any effects on plasma insulin (6,
26, 30). These cytokines all stimulated lipolysis. Despite this massive
and comparable endocrine response, IL-6 stimulates peripheral uptake of
glucose, whereas the same response induces insulin resistance after
TNF- administration and without any influences on glucose metabolism
after IFN-. These effects of TNF-, IL-6, and IFN- coincide
with an increase in resting energy expenditure.
The differences in endocrine and metabolic effects between IFN- and
the other cytokines cannot be ascribed to differences in the amount of
cytokine administrated. The molar amount of IFN- administered in the
present study (6.1 nmol/m2) was
higher than the amounts of TNF-, IFN-, and IL-6 administered in
our previous studies in humans (2.8, 1.3, and 3.8 nmol/m2, respectively) (6, 26,
30). The serum levels reached in these previous studies were in the
same range as in the present IFN- study (IFN- 3.1 × 102 pmol/ml vs. 2.8 and 6.2 × 103 pmol/ml for
IL-6 and IFN-, respectively); TNF- levels were higher because of
intravenous, bolus administration and are therefore not suited to this
molar comparison (13).
The question arises as to whether the only metabolic effect induced by
IFN-, an increase of ~11% in resting energy expenditure, may have
clinical implications. No straightforward conclusion can be drawn,
because it has been shown that an increase in resting energy
expenditure by itself does not necessarily induce changes in body
composition. This is exemplified by the metabolic changes found in the
different stages of human immunodeficiency virus infection. In both the
asymptomatic phase and in the symptomatic phase of this disease, an
increase in resting energy expenditure by ~10% is found with
major differences in other metabolic parameters between both disease
stages (10, 11).
It can be concluded that the proinflammatory cytokine IFN- is not a
stimulator of endocrine and metabolic pathways, at least in comparison
with IL-6, IFN-, and TNF-. Therefore, IFN- by itself is
probably not a major mediator in the interaction between the immune and
the endocrine and metabolic systems. However, we cannot exclude the
possibility that IFN-, along with other mediators released during
infection, may have a synergistic effect on the endocrine
and/or metabolic system.
| |
ACKNOWLEDGEMENTS |
|---|
We thank the Laboratory of Endocrinology and the Clinical and Laboratory Immunology Unit for excellent analytical support.
| |
FOOTNOTES |
|---|
J. A. Romijn is supported by the Netherlands Organisation for Scientific Research (NWO) and the Dutch Diabetes Foundation.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests: J. A. Romijn, Dept. of Internal Medicine, F4-222 Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, The Netherlands (E-mail: j.demetz{at}amc.uva.nl).
Received 18 June 1998; accepted in final form 13 October 1998.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
1.
Basham, T. Y.,
and
T. C. Merigan.
Recombinant interferon-gamma increases HLA-DR synthesis and expression.
J. Immunol.
130:
1492-1494,
1983[Abstract].
2.
Becker, S.
Interferons as modulators of human monocyte-macrophage differentiation. I. Interferon-gamma increases HLA-DR expression and inhibits phagocytosis of zymosan.
J. Immunol.
132:
1249-1254,
1984[Abstract].
3.
Blalock, J. E.
The syntax of immune-neuroendocrine communication.
Immunol. Today
15:
504-511,
1994[Medline].
4.
Chambrier, C.,
A. Mercatello,
E. Tognet,
J. M. Cottet-Emard,
R. Cohen,
J. Y. Blay,
M. Favrot,
T. Philip,
and
M. Beylot.
Hormonal and metabolic effects of chronic interleukin-2 infusion in cancer patients.
J. Biol. Response Mod.
9:
251-255,
1990[Medline].
5.
Chrousos, G. P.
The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation.
N. Engl. J. Med.
332:
1351-1362,
1995
6.
Corssmit, E. P.,
R. Heijligenberg,
E. Endert,
M. T. Ackermans,
H. P. Sauerwein,
and
J. A. Romijn.
Endocrine and metabolic effects of interferon-alpha in humans.
J. Clin. Endocrinol. Metab.
81:
3265-3269,
1996[Abstract].
7.
Friedman, A. L. Growth hormone is not safe for
children with renal transplants. J. Pediatr. 131, Suppl.:
S25-S27, 1997.
8.
Goldstein, D.,
J. Gockerman,
R. Krishnan,
J. Ritchie, Jr.,
C. Y. Tso,
L. E. Hood,
E. Ellinwood,
and
J. Laszlo.
Effects of gamma-interferon on the endocrine system: results from a phase I study.
Cancer Res.
47:
6397-6401,
1987
9.
Holsboer, F.,
G. K. Stalla,
U. von Bardeleben,
K. Hammann,
H. Muller,
and
O. A. Muller.
Acute adrenocortical stimulation by recombinant gamma interferon in human controls.
Life Sci.
42:
1-5,
1988[Medline].
10.
Hommes, M. J.,
J. A. Romijn,
E. Endert,
J. K. Eeftinck Schattenkerk,
and
H. P. Sauerwein.
Basal fuel homoeostasis in symptomatic human immunodeficiency virus infection.
Clin. Sci. (Colch).
80:
359-365,
1991[Medline].
11.
Hommes, M. J.,
J. A. Romijn,
E. Endert,
and
H. P. Sauerwein.
Resting energy expenditure and substrate oxidation in human immunodeficiency virus (HIV)-infected asymptomatic men: HIV affects host metabolism in the early asymptomatic stage.
Am. J. Clin. Nutr.
54:
311-315,
1991
12.
Imura, H.,
and
J. Fukata.
Endocrine-paracrine interaction in communication between the immune and endocrine systems. Activation of the hypothalamic-pituitary-adrenal axis in inflammation.
Eur. J. Endocrinol.
130:
32-37,
1994[Abstract].
13.
Koopmans, R.,
F. J. Hoek,
S. J. van Deventer,
and
T. Van der Poll.
Model for whole body production of tumour necrosis factor-alpha in experimental endotoxaemia in healthy subjects.
Clin. Sci. (Colch).
87:
459-465,
1994[Medline].
14.
Kox, W. J.,
R. C. Bone,
D. Krausch,
W. D. Docke,
S. N. Kox,
H. Wauer,
K. Egerer,
S. Querner,
K. Asadullah,
R. von Baehr,
and
H. D. Volk.
Interferon gamma-1b in the treatment of compensatory anti-inflammatory response syndrome. A new approach: proof of principle.
Arch. Intern. Med.
157:
389-393,
1997[Abstract].
15.
Kragsbjerg, P.,
T. Vikersfors,
and
H. Holmberg.
Serum levels of interleukin-6, tumor necrosis factor-alpha, interferon-gamma and C-reactive protein in adults with community-acquired pneumonia.
Serodiagn. Immunoth. Infect. Disease
5:
156-160,
1993.
16.
Krouwels, F. H., B. E. Hol, B. Bruinier, R. Lutter, H. M. Jansen, and T. A. Out. Cytokine
production by T-cell clones from bronchoalveolar lavage fluid of
patients with asthma and healthy subjects. Eur.
Respir. J. 22, Suppl.: 95S-103S, 1996.
17.
Livingston, D. H.,
P. A. Loder,
S. M. Kramer,
U. E. Gibson,
and
H. C. Polk, Jr.
Interferon gamma administration increases monocyte HLA-DR antigen expression but not endogenous interferon production.
Arch. Surg.
129:
172-178,
1994[Abstract].
18.
McEwen, B. S.,
C. A. Biron,
K. W. Brunson,
K. Bulloch,
W. H. Chambers,
F. S. Dhabhar,
R. H. Goldfarb,
R. P. Kitson,
A. H. Miller,
R. L. Spencer,
and
J. M. Weiss.
The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions.
Brain Res. Brain Res. Rev.
23:
79-133,
1997[Medline].
19.
Pajkrt, D.,
L. Camoglio,
M. C. Tiel-van Buul,
K. de Bruin,
D. L. Cutler,
M. B. Affrime,
G. Rikken,
T. Van der Poll,
J. W. ten Cate,
and
S. J. van Deventer.
Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia: effect of timing of recombinant human IL-10 administration.
J. Immunol.
158:
3971-3977,
1997[Abstract].
20.
Ramshaw, I. A.,
A. J. Ramsay,
G. Karupiah,
M. S. Rolph,
S. Mahalingam,
and
J. C. Ruby.
Cytokines and immunity to viral infections.
Immunol. Rev.
159:
119-135,
1997[Medline].
21.
Reinauer, H.,
F. A. Gries,
A. Hubinger,
O. Knode,
K. Severing,
and
F. Susanto.
Determination of glucose turnover and glucose oxidation rates in man with stable isotope tracers.
J. Clin. Chem. Clin. Biochem.
28:
505-511,
1990[Medline].
22.
Rossol, S.,
R. Voth,
H. P. Laubenstein,
W. E. Muller,
H. C. Schroder,
K. H. Meyer zum Buschenfelde,
and
G. Hess.
Interferon production in patients infected with HIV-1.
J. Infect. Dis.
159:
815-821,
1989[Medline].
23.
Smedes, F.,
J. C. Kraak,
and
H. Poppe.
Simple and fast solvent extraction system for selective and quantitative isolation of adrenaline, noradrenaline and dopamine from plasma and urine.
J. Chromatogr.
231:
25-39,
1982[Medline].
24.
Spath-Schwalbe, E.,
F. Porzsolt,
W. Digel,
J. Born,
B. Kloss,
and
H. L. Fehm.
Elevated plasma cortisol levels during interferon-gamma treatment.
Immunopharmacology
17:
141-145,
1989[Medline].
25.
Starnes, H. F., Jr.,
R. S. Warren,
M. Jeevanandam,
J. L. Gabrilove,
W. Larchian,
H. F. Oettgen,
and
M. F. Brennan.
Tumor necrosis factor and the acute metabolic response to tissue injury in man.
J. Clin. Invest.
82:
1321-1325,
1988.
26.
Stouthard, J. M.,
J. A. Romijn,
T. Van der Poll,
E. Endert,
S. Klein,
P. J. Bakker,
C. H. Veenhof,
and
H. P. Sauerwein.
Endocrinologic and metabolic effects of interleukin-6 in humans.
Am. J. Physiol.
268 (Endocrinol. Metab. 31):
E813-E819,
1995
27.
Troppmair, J.,
K. Nachbaur,
M. Herold,
W. Aulitzky,
H. Tilg,
G. Gastl,
P. Bieling,
B. Kotlan,
R. Flener,
B. Mull,
W. O. Aulitzky,
H. Rokkos,
and
C. Huber.
In-vitro and in-vivo studies on the induction of neopterin biosynthesis by cytokines, alloantigens and lipopolysaccharide (LPS).
Clin. Exp. Immunol.
74:
392-397,
1988[Medline].
28.
Vahouny, G. V.,
E. Kyeyune-Nyombi,
J. P. McGillis,
N. S. Tare,
K. Y. Huang,
R. Tombes,
A. L. Goldstein,
and
N. R. Hall.
Thymosin peptides and lymphokines do not directly stimulate adrenal corticosteroid production in vitro.
J. Immunol.
130:
791-794,
1983[Abstract].
29.
Van der Hoorn, F. A.,
F. Boomsma,
A. J. Man in 't Veld,
and
M. A. Schalekamp.
Determination of catecholamines in human plasma by high-performance liquid chromatography: comparison between a new method with fluorescence detection and an established method with electrochemical detection.
J. Chromatogr.
487:
17-28,
1989[Medline].
30.
Van der Poll, T.,
J. A. Romijn,
E. Endert,
J. J. Borm,
H. R. Buller,
and
H. P. Sauerwein.
Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans.
Am. J. Physiol.
261 (Endocrinol. Metab. 24):
E457-E465,
1991
31.
Vankelecom, H.,
P. Carmeliet,
H. Heremans,
J. Van Damme,
R. Dijkmans,
A. Billiau,
and
C. Denef.
Interferon-gamma inhibits stimulated adrenocorticotropin, prolactin and growth hormone secretion in normal rat anterior pituitary cell cultures.
Endocrinology
126:
2919-2926,
1990[Abstract].
32.
Waage, A.,
and
S. Steinshamn.
Cytokine mediators of septic infections in the normal and granulocytopenic host.
Eur. J. Haematol.
50:
243-249,
1993[Medline].
33.
Weller, M.,
A. Stevens,
N. Sommer,
A. Melms,
J. Dichgans,
and
H. Wietholter.
Comparative analysis of cytokine patterns in immunological, infectious and oncological neurological disorders.
J. Neurol. Sci.
104:
215-221,
1991[Medline].
34.
Wenischj, C.,
B. Parschalk,
E. Narzt,
S. Looareesuwan,
and
W. Graninger.
Elevated serum levels of IL-10 and IFN-gamma in patients with acute Plasmodium falciparum malaria.
Clin. Immunol. Immunopathol.
74:
115-117,
1995[Medline].
35.
Wilder, R. L.
Neuroendocrine-immune system interactions and autoimmunity.
Annu. Rev. Immunol.
13:
307-338,
1995[Medline].
This article has been cited by other articles:
|
|
 |
|
  E. P. Zorrilla, M. Sanchez-Alavez, S. Sugama, M. Brennan, R. Fernandez, T. Bartfai, and B. Conti Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency PNAS, June 26, 2007; 104(26): 11097 - 11102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. de Metz, J. A. Romijn, E. Endert, M. T. Ackermans, G. J. Weverling, O. R. Busch, L. Th. de Wit, D. J. Gouma, I. J. M. t. Berge, and H. P. Sauerwein Interferon-{gamma} increases monocyte HLA-DR expression without effects on glucose and fat metabolism in postoperative patients J Appl Physiol, February 1, 2004; 96(2): 597 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. H. Eurlings, C. J. H. van der Kallen, J. M. W. Geurts, P. Kouwenberg, W. D. Boeckx, and T. W. A. de Bruin Identification of differentially expressed genes in subcutaneous adipose tissue from subjects with familial combined hyperlipidemia J. Lipid Res., June 1, 2002; 43(6): 930 - 935. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
) vs. saline administration (
) are shown. Values
are means ± SE. bpm, Beats/min.
P < 0.05 vs. corresponding
value on control day.
