Anti-inflammatory Action of Erythromycin*

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Ficuax 1. Changes in neutrophil NADPH oxidase activities in
whole-cell system of patients receiving erythromycin. Control
NADPH oxidase activity in neutrophils from normal subjects was
20.5 ± 2.6 (mean ± SD; n = 6) nmol/10’ cells per minute. Results are
means of two different experiments.
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free system (Fig 2B) are shown in Figure 2. Erythromycin
concentration dependently inhibited NADPH
oxidase activities in both whole-cell and cell-free
systems, and the concentration of the drug required
for 50 percent inhibition of oxidase (IC30) was 0.7 mM
in the whole-cell system and 0.2 mM in the cell-free
system; however, the methanol concentrations of less
than 125 mM produced no significant effect on
NADPH oxidase activities, both in the whole-cell and
the cell-free systems (data not shown). The IC30 value
for the methanol alone required a concentration of
more than 500 mM in both systems (data not shown).
In experiments with erythromycin at different concentrations
in 80 mM methanol both in the whole-cell
and cell-free systems, there were no significant
changes in NADPH oxidase activities (data not shown).
In addition, the drug at a concentration required to
obtain IC30 did not change the Kin value for the
substrate NADPH of the oxidase (data not shown).
DISCUSSION
Human neutrophils are a major component of the
body’s defense against microbial invasion;’4 however,
neutrophils are also important in the pathogenesis of
inflammation or tissue damage in certain postinfectious
or noninfectious diseases. The cells are activated
by phagocytic stimuli or high amounts of microbicidal
oxidants, leading to production of superoxide through
the activation of plasma membrane-bound NADPH
oxidase. Several reports concerning the effects of
therapeutic drugs on NADPH oxidase have been
0 100 200 300 ‘400 500 600
Concentration of drug (hiM)
FIGURE 2. Effects oferythromycin in vitro on superoxide production
of intact stimulated neutrophils in whole-cell system (A) and on
activation of NADPH oxidase in cell-free system (B). In both
systems, neutrophils from normal subjects were employed. Control
activities in whole-cell and cell-free systems are 20.5 ± 2.6 (mean
± SD; n = 6) nmol/10’ cells per minute and 19.6 ± 2.3 (mean ± SD;
n = 4) nmol/10 cells per minute, respectively. Results are means
(± SD) ofthree different experiments.
presented. My colleagues and U0,” previously reported
that steroids and nonsteroidal anti-inflammatory
drugs inhibit the NADPH oxidase from human
neutrophils in whole-cell and cell-free systems.
Recent studies have suggested biological and biochemical
actions other than simple antimicrobial activity
in some antibiotics. Goswami et al’5 demonstrated
that erythromycin may inhibit respiratory glycoconjugate
secretion from the mucosa of human airways in
vitro. Ichikawa et al6 reported that erythromycin may
reduce in vitro neutrophils and neutrophil-derived
elastolytic-like activity in the bronchoalveolar lavage
fluid obtained from patients with bronchiolitis.
Anderson5 reported that the drug may inhibit the
generation of superoxide by neutrophils exposed to
stimulating agents using a chemiluminescence technique;
however, little information about the effects of
erythromycin on the activation of NADPH oxidase in
cell-free systems is available.
In Japan, several investigators have found oral erythromycin
clinically effective for bronchiolitis, an Un-
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1192 Anti-inflammatory Action of Erythromycin (Shigenobu Umeki)
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