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Dose-dependent enhancements by interferon-gamma on functional responses of
neutrophils from chronic granulomatous disease patients
A Ahlin, G Elinder and J Palmblad
Department of Pediatrics, The Karolinska Institute at Sachs' Children's
Hospital, Stockholm, Sweden.
Interferon-gamma (IFN-gamma) is recommended as prophylaxis against
infections in patients with chronic granulomatous disease (CGD). However,
since the optimal dose, the dosing interval, and the mechanisms of action
are not well-defined, we studied the effects on CGD neutrophil (PMN)
functions ex vivo of interferon-gamma (IFN-gamma). Evaluations were made on
oxidative capacity, measured by superoxide anion production and
chemiluminescence after stimulation with f-met-leu- phe (f-MLP) or
phorbol-myristate-acetate, the killing of Aspergillus fumigatus hyphae
(assessed as conversion of the tetrazolium salt MTT to formazan), and on
the expression of Fc gammaRI receptor (CD64). After randomization, 9 CGD
patients (4 with gp91phox, 3 with p47phox, 1 with p67phox deficiency and 1
with unspecified CGD) were given IFN-gamma, either 50 or 100 microg/m2
subcutaneously on 2 consecutive days after double blinded randomization.
Furthermore, one female hyperlyonized X- linked carrier with a CGD
phenotype was also studied separately after IFN-gamma treatment.
Evaluations were made the day before and on days 1, 3, 8, and 18 after
IFN-gamma administration. The killing of A fumigatus hyphae, being close to
zero before IFN-gamma, was enhanced on day 3, being 36% higher than
pretreatment values in the high-dose CGD group and 17% in the low-dose
group. The expression of Fc gammaRI on PMN increased 3.7-fold in the
high-dose and 2.3-fold in the low-dose CGD group, being maximal on day 1.
Oxidative functions were raised in only selected patients represented by
different subtypes of CGD. The hyperlyonized carrier of X-linked CGD
responded to IFN-gamma with more enhanced oxidative responses and
Aspergillus killing of her PMNs than the other patients. This study
suggests that a higher dose of IFN-gamma than currently recommended confers
transient enhancements of certain PMN functions in CGD patients.
Volume 89,
Issue 9,
pp. 3396-3401,
05/01/1997
Copyright © 1997 by The American Society of Hematology
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