Impairment of the hematological response and interleukin-1β production in protein-energy malnourished mice after endotoxemia with lipopolysaccharide

R.A Fock,P Borelli,M.A.R Vinolo,S.L Blatt

doi:10.1590/s0100-879x2012007500151

Abstract

The objectives of this study were to determine if protein-energy malnutrition (PEM) could affect the hematologic response to lipopolysaccharide (LPS), the interleukin-1β (IL-1β) production, leukocyte migration, and blood leukocyte expression of CD11a/CD18. Two-month-old male Swiss mice were submitted to PEM (N = 30) with a low-protein diet (14 days) containing 4% protein, compared to 20% protein in the control group (N = 30). The total cellularity of blood, bone marrow, spleen, and bronchoalveolar lavage evaluated after the LPS stimulus indicated reduced number of total cells in all compartments studied and different kinetics of migration in malnourished animals. The in vitro migration assay showed reduced capacity of migration after the LPS stimulus in malnourished animals (45.7 ± 17.2 × 104 cells/mL) compared to control (69.6 ± 7.1 × 104 cells/mL, P ≤ 0.05), but there was no difference in CD11a/CD18 expression on the surface of blood leukocytes. In addition, the production of IL-1β in vivo after the LPS stimulus (180.7 pg·h−1·mL−1), and in vitro by bone marrow and spleen cells (41.6 ± 15.0 and 8.3 ± 4.0 pg/mL) was significantly lower in malnourished animals compared to control (591.1 pg·h−1·mL−1, 67.0 ± 23.0 and 17.5 ± 8.0 pg/mL, respectively, P ≤ 0.05). The reduced expression of IL-1β, together with the lower number of leukocytes in the central and peripheral compartments, different leukocyte kinetics, and reduced leukocyte migration capacity are factors that interfere with the capacity to mount an adequate immune response, being partly responsible for the immunodeficiency observed in PEM.

Highlights

IntroductionProtein energy malnutrition (PEM)-mediated impairment of the immune system results in increased morbidity and mortality due to infectious complications [1,2]
Protein energy malnutrition (PEM) is the most frequent type of malnutrition affecting millions of people worldwide, especially children, underweight newborn infants, the elderly, individuals with eating disorders such as nervous anorexia and bulimia, patients with neoplasias or chronic diseases, patients under chemotherapy or hospitalized patients of advanced age (≥60 years), and individuals who undergo radical diets [1,2,3].PEM-mediated impairment of the immune system results in increased morbidity and mortality due to infectious complications [1,2]
The LPS stimulus reduced the number of leukocytes in the control group (P ≤ 0.05) after 2 h, but an increase of the neutrophilic lineage was observed in the control group 24 h after the LPS stimulus

Summary

Introduction

PEM-mediated impairment of the immune system results in increased morbidity and mortality due to infectious complications [1,2]. PEM modifies physiological responses and may induce cellular lesions, and the extent and timing of damage differs depending on the tissue. The elevated and constant protein demand of hematopoietic tissue leads to a condition in which both qualitative and quantitative alterations may be found when PEM occurs. PEM modifies both the adaptive and innate immune response of organisms to infectious agents, such as a reduced production of blood cells, thereby leading to bone marrow hypoplasia and the induction of structural alterations in bone marrow [4,5,6,7,8]

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