Improvement of superoxide production in monocytes from patients with
chronic granulomatous disease by recombinant cytokines
V Jendrossek, AM Peters, S Buth, J Liese, U Wintergerst, BH Belohradsky and M Gahr
Universitatskinderklinik Gottingen, Germany.
Cytokines have been shown to modulate the respiratory burst of
polymorphonuclear leukocytes and monocytes from normal controls. We have
examined whether monocytes from children with chronic granulomatous disease
(CGD) can be primed by cytokines other than interferon-gamma (IFN gamma),
which has been demonstrated to improve the production of reactive oxygen
species in vivo and in vitro. Monocytes isolated from peripheral blood were
cultured without and with IFN gamma (500 U/mL), tumor necrosis factor-alpha
(500 U/mL), interleukin-1 beta (IL-1 beta) (100 U/mL), and IL-3 (100 U/mL).
After 3 days of culture, the phorbolmyristate acetate (2 ng/mL) and the
formyl- methionyl-leucyl-phenylalanine (0.1 mumol/L)-stimulated superoxide-
production was determined in a microtiter system. In nearly all of the 14
patients examined (5 autosomal, 5 X-chromosomal, and 4 of unknown
inheritance), an improvement of superoxide production could be
demonstrated. The most impressive effect with the cytokines newly tested
was seen with monocytes from autosomal CGD patients treated with IL-3 and
stimulated by phorbolmyristate acetate. In single patients cultivation of
monocytes with IL-6 and granulocyte-macrophage colony- stimulating factor
resulted in only slight improvement of superoxide production. Our findings
indicate that cytokines other than IFN gamma can positively modulate the
defective respiratory burst in CGD and that each patient reacts with an
individual pattern to different cytokines.
Volume 81,
Issue 8,
pp. 2131-2136,
04/15/1993
Copyright © 1993 by The American Society of Hematology