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A Candida albicans corneal ulcer developed in a 24-year-old man with a history
of eczema, asthma, and multiple bacterial infections since childhood. The
infection responded well to oral flucytosine (12 g/day for 15 days) and topical
amphotericin B. Positive laboratory findings included eosinophilla,
hyperimmunoglobulinemia E, and impaired neutrophil and monocyte spontaneous
migration and chemotactic responses. Ascorbic acid corrected the monocyte defect
in vitro and in vivo, but had no effect on neutrophil function.

2 children with undue susceptibility to skin infections and isolated defective
neutrophil bacterial killing are described. Since the NBT-reducing capabilities
of granulocytes were normal, a mild form of chronic granulomatous disease was
excluded. Ascorbic acid was effective in delaying and eventually suppressing
infectious episodes.

Ten patients with neutrophil dysfunctions and recurrent pyogenic infections,
mainly of the skin middle-ear, and respiratory tract, are described. The most
frequently affected functions were chemotaxis and bacterial killing.
Pharmacologic restoration of functional defects was tried in all cases.
Levamisole was given in two cases and ascorbic acid in the other eight cases.
During a follow up of at least 18 months, seven patients showed a complete
restoration of neutrophil function and a long-lasting clinical remission. One of
the two patients with Chronic Granulomatous Disease has been free from
infections for 1 year, despite persistent neutrophil dysfunction, while the
other did not display consistent clinical improvement. Another patient, who was
given ascorbic acid for a short period only due to non compliance, showed
neither laboratory nor clinical improvement.

Ascorbic acid is able to stimulate neutrophil oxidative metabolism in normal
neutrophils, as well as other several functions of these cells, either in the
normal state or in the defective one. In the present study, we have investigated
the effects of ascorbic acid on the hexose monophosphate shunt (HMPS) and on the
bactericidal activity of neutrophils from Chronic Granulomatous Disease (CGD)
patients. Furthermore, we have investigated the effects of ascorbic acid on the
antibody dependent cell cytotoxicity (ADCC) of normal neutrophils. Ascorbic acid
in vitro was able to significantly improve both HMPS activity and bacterial
killing of CGD neutrophils. Its prolonged administration to such patients led to
consistent clinical improvement, possibly related to the enhancement of
chemotaxis, although the effects on HMPS and bacterial killing seen in vitro
could not be confirmed. Ascorbic acid was also able to interfere with neutrophil
ADCC with different results depending on its concentration and the experimental
conditions.

Neutrophil function was studied in several patients with recurrent infections,
mainly of the skin. Twelve patients showed impairment of neutrophil functions,
either chemotaxis or bacterial killing and phagocytosis. Levamisole was given in
four cases: improvement of neutrophil function and long-lasting clinical
remission occurred in three of them, whilst in the fourth the drug was not
tolerated. Ascorbic acid was administered to three other patients, with
satisfactory improvement of neutrophil function and long-lasting clinical
remission.

We have investigated the effects of supplementation of the diet with the
antioxidant vitamins C and E on several functions of the immune response of aged
women. Ten healthy women and 20 women (72 6 years old) suffering two
diseases often associated with age (10 with major depression disorders, MDD, and
10 with coronary heart disease, CHD) were administered 1 g of vitamin C and 200
mg of vitamin E daily for 16 weeks. Blood samples were collected before and
after treatment for measurement of several immunological functions, namely
proliferative response of lymphocytes to the mitogen phytohemagglutinin (20
mg/L) and phagocytic functions of polymorphonuclear (PMN) neutrophils, i.e.,
adherence to vascular endothelium, chemotaxis, phagocytosis of latex beads, and
superoxide anion production. In addition, we also determined the levels of serum
cortisol and lipid peroxides. Intake of vitamins resulted in a significant
increase in the lymphoproliferative capacity and in the phagocytic functions of
PMN neutrophils as well as in a significant decrease of serum levels of lipid
peroxides and cortisol, both in the healthy aged women and in the aged women
with MDD or CHD. These findings suggest an important role of antioxidant
supplementation in the improvement of immune function in aged females as well as
in the prevention and treatment of specific diseases associated with age that
are quite prevalent in the developed countries.

BACKGROUND. Neutrophils play a critical role in host defense against a variety
of microbial pathogens. There is much information to suggest a role for vitamin
C in the physiology of neutrophils. Thus, the effects of vitamin C treatment
were studied in a patient with a history of recurrent furunculosis who showed
altered neutrophil functions. METHODS. Superoxide generation was measured by
cytochrome C reduction. Phagocytosis of opsonized zymosan by neutrophils and
chemotaxis on agarose plates were determined. RESULTS. Chemotaxis, phagocytosis,
and superoxide generation of the patient's neutrophils were significantly lower
than those of the matched control. Treatment with vitamin C (500 mg/day) for 30
days caused a dramatic clinical response and a significant improvement of all
three neutrophil functions to values similar to those of the controls.
CONCLUSIONS. We suggest that the patient described here had a temporary defect
in neutrophil functions. The treatment with vitamin C probably prevented
neutrophil oxidation, thus contributing to recovery of neutrophil function and
arrest of furunculosis.

Neutrophil migration, postphagocytic hexose-monophosphate shunt activity and
myeloperoxidase-mediated iodination of ingested Candida albicans and lymphocyte
mitogen-induced transformation were assessed in six normal volunteers before and
1 h after a single intravenous injection of 1 g ascorbate. Increased neutrophil
motility was observed which was associated with decreased
myeloperoxidase-mediated iodination of C. albicans and a slight increase in
hexose-monophosphate shunt activity. Lymphocyte transformation was also
increased. Alterations in these activities were related to serum ascorbate
levels. To investigate the relationship of ascorbate-mediated increased
neutrophil motility and lymphocyte transformation to decreased peroxidase
activity neutrophils and lymphocytes from normal individuals were exposed to the
horseradish peroxidase/H2O2/sodium iodide system in the presence and absence of
ascorbate and tested for migratory and proliferative responses respectively.
Exposure to the horseradish peroxidase/H2O2/halide system caused inhibition of
neutrophil motility and lymphocyte responsiveness to mitogens. However,
inclusion of ascorbate protected both the neutrophils and lymphocytes from the
inhibitory effects of the horseradish peroxidase/H2O2/halide system.

The aim of the present work is to study the change with aging in the effect in
vitro of several antioxidants: thiazolidine-4-carboxylic acid or thioproline,
N-acetylcysteine (NAC), ascorbic acid (AA), and alpha-tocopherol (vitamin E, VE)
on the natural killer (NK) activity in mononuclear cells from axillary nodes,
spleen, thymus and peritoneal leukocytes from BALB/c male mice. Young (82
weeks), adult (242 weeks). mature (482 weeks), and old (722 weeks)
animals were studied. A nonradioactive cytotoxic assay with cells from the
murine lymphoma YAC-1 as target cells and a relation effector cells/target cells
of 10/1 were used. The concentrations of the different antioxidants were: 1 mM
for thioproline and N-acetylcysteine and 5 microM for ascorbic acid and
alpha-tocopherol, which induced a maximum effect in our previous dose-response
experiments. The results show that, in general, the above antioxidants cause an
enhancement of the NK activity at all ages studied, this stimulation being
higher with thioproline and N-acetylcysteine than with ascorbic acid and
alpha-tocopherol. The effects were similar for the three lymphoid organs and the
peritoneum. This stimulation of the NK activity by antioxidants is an important
favorable response, especially in old mice, in which age results in a decrease
in NK function and, therefore, in a higher incidence of neoplasia.

After exposure to many toxic chemicals, NK function can be decreased
significantly. Weeks or months later, natural killer (NK) function can rebound
to normal levels in some and can be suppressed for prolonged periods of time in
other patients. In view of this, we decided to study the effect of buffered
vitamin C on NK, T and B cell function in patients who had been exposed to toxic
chemicals. After the first blood draw, 55 patients immediately ingested
granulated buffered vitamin C in water at a dosage of 60 mg/Kg body weight.
Exactly 24 hours later, blood was again drawn for a follow-up study of NK, T and
B cell function. Vitamin C in high oral dose was capable of enhancing NK
activity up to ten-fold in 78% of patients. Lymphocyte blastogenic responses to
T and B cell mitogens were restored to the normal level after vitamin C usage.
Signal transduction enzyme protein kinase C (PKC) appeared to be involved in the
mechanism of induction of NK activity by vitamin C. We conclude that immune
functional abnormalities can be restored after toxic chemical exposure by oral
usage of vitamin C.