Maya

Das,4

Stephen

M.D.,

A. Feig,7

Ph.D.,

E. Richard

M.D.,

Thomas

Borut,6

M.D.,

in

and

M.D.

ABSTRACT

Mononuclear

phosphoglycerate kinase well with the percentage nm

Stiehm,5

dysfunction

causes

an

The

correlation

are

immediate

cells

increase

of PK

of

and pyruvate of circulating activity

with

in distinct

contrast

relationship

of the

to observed

malnutrition

has not yet been

metabolic

malnourished

in PK

activity

T-cells

and

response

cells of PK

of neonatal to the Am.

defined.

contain

diminished

activity

of

The PK activity of these cells correlates lymphocytes (T-cells). Phytohemaggluti-

of mononuclear the

perturbations alterations

Infection is a major cause of morbidity and mortality in the malnourished patient. Several lines of evidence support the concept that the increased rate and severity of infection in malnutrition is a result of impaired cellular immunity: Smythe et al. (1) has observed thymolymphatic atrophy as a result of severe protein-calorie malnutrition, and several workers have demonstrated impaired delayed cutaneous hypersensitivity responses in malnourished patients (2-4). These clinical observations have been correlated with a relative and absolute diminution in the size of the thymus-derived-lymphocyte (T-cell) compartment (1-6). The degree of T-cell depletion is proportional to the severity of malnutrition (5) and is accompanied by an impairment of mitogen-induced proliferation (2, 4-6). The studies reported here were undertaken in an effort to delineate the metabolic basis of immunocyte function and to determine whether metabolic perturbations of lymphocytes could be detected in the immunodeficiency of malnutrition.

children

kinase (PK). thymus-derived

Nutr.

cell of

30:

patients.

to phytohemagglutinin

mononuclear

pathophysiology

J. Clin.

of malnourished

activity

the

metabolism.

immune

1949-1952,

The

system

in

1977.

nervosa (in one patient), and severe failure to thrive (no final specific diagnosis in three patients). Anthropomorphic data on these patients is shown in Table 1. Circulating mononuclear cells were isolated by ficoll-isopaque density gradient centrifugation (7). The cells were washed once in a balanced salt solution, counted manually, and their viability tested by trypan blue exclusion (8). The cell population was >95% mononuclear, with 10 to 20% monocytes. Contamination with erythrocytes and platelets was negligible. A suspension of cells (0.1 to 1 .0 x 106/ml) was subjected to ultrasonic disruption for use in the enzyme assays. Enzyme assays were performed in a final volume of 1.0 ml in a Gilford Recording Spectrophotometer. Pyruvate kinase (PK) activity was measured in a system containing 100 mM Tris-HC18 (pH 8.0), 10 msi MgCl2, 100 mM KC1, 1.5 mst phosphoenolpyruvate,9 0.4 mM ADP,8 0.2 mst NADH,8 and 6u lactic dehydrogenase.9 Phosphoglycerate kinase (PGK) activity was measured in a system containing 100 mM Tris-HCI8 (pH 8.0), 10 mM MgCI2, 0.2 msi NADH,8 5 msi ATP,8 1 mst 3phosphoglycerate9 and 4u glyceraldehyde phosphate dehydrogenase . Adenylate kinase (AK) activity was measured in a system containing 100 msi Tris-HC18 (pH 8.0), 50 msi MgCI2, 20 msi KCI, 0.75 mM

‘From the Gwynne Hazen Cherry Memorial ratory and the Department of Pediatrics. School of Medicine, Los Angeles, Calif. 90024. 2 Supported in part by Grants from the

States

Public

Health

Service

(RR-5354,

LaboUCLA United

HD 09800-

02)

Materials

and

methods

Defibrinated blood samples were obtained from 50 normal adults and 13 patients with malnutrition. Only one malnourished patient was under a year of age. Malnutrition was due to exogenous protein-calorie malnutrition (in three subjects), severe gastrointestinal disease and malabsorption (in six subjects), anorexia

The

American

Journal

of

and by the Karen Brigham Memorial Fund. Address reprint requests to: S. A. Feig, M.D., Department of Pediatrics, UCLA School of Medicine, Los Angeles, Calif. 90024. 4Fellow in Pediatric Hematology-Oncology. Professor of Pediatrics. in Pediatric Immunology. Assistant Professor of Pediatrics. Chemical Co., St. Louis, Mo. 9Boehringer Mannheim Corp., San Francisco, Calif. ‘

Clinical

Nutrition

30: DECEMBER

1977,

pp. 1949-1952.

Printed

in U .S.A.

1949

Downloaded from https://academic.oup.com/ajcn/article-abstract/30/12/1949/4650836 by East Carolina University user on 13 January 2019

Metabolic correlates of immune malnourished children13

DAS

1950

TABLE

ET AL.

1

Anthropomorphic

data

on

malnutrition

Age/sex

patients

Diagnosis

studied Height

(cm)

Weight

(Percentile)’

(kg)

Total

(Percentile)’

% Circulating

protein/albumin

T cells’

1.

18

mo/male

Protein-calorie malnutrition Protein-calorie malnutrition Protein-calorie malnutrition Malabsorption Failure to thrive Malabsorption Anorexia nervosa Failure to thrive Malabsorption Malabsorption Malabsorption Malabsorption Failure to thrive

5 mo/male

2. 3.

2’h

yr/female

4. 9 yr/male 5. 1 yr/female 6. 17 mo/female 7. 16 yr/female 8. 4 yr/female 9. 2V yr/male 10. 13 mo/female 11. 16 mo/female 12. 9 yr/male 13. 6 yr/male National

#{176}

(HRA)

76-1

Center 120.

for Health

Health

Resources

Statistics Growth Administration,

72 (