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

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.

Protein Malnutrition Alters Spleen Cell Proliferation and IL-2 and IL-10 Production by Affecting the STAT-1 and STAT-3 Balance

“…Evidence indicates that leukopenia is common in situations in which malnutrition is associated with other diseases [24][25][26]. In this study, the malnourished animals showed a reduced number of blood leukocytes and a hypoplastic spleen with reduced cellularity and increased capsule thickness.…”

“…States of nutritional deficiency alter the defense mechanisms of an individual and include malnutrition, which is a major health problem with serious consequences on the body such as metabolic imbalance, neurological changes, and alterations of lymphoid organs, predisposing to the individual to infectious diseases [4,24].…”

Avaliação de aspectos regulatórios da hematopoese em desnutrição proteico-energética experimental: papel das células endoteliais derivadas das células tronco mesenquimais medulares

“…As informações da literatura são conflitantes com relação a dietas hipoproteicas e consumo de ração; alguns trabalhos mostram aumento de consumo (COLOMBO et al, 1992;WHITE et al, 1998;NAKAJIMA et al, 2014), enquanto outros relatam comportamento anorético dos animais (BECK et al, 1989;MERCER et al, 1994). Este comportamento em relação à redução na ingestão de ração hipoproteica era esperado, visto que esta reação é habitual em outros trabalhos realizados por nosso grupo (BORELLI et al, 2004;BORELLI et al, 2007;FOCK et al, 2008;BORELLI et al, 2009;FOCK, BLATT, et al, 2010;FOCK, ROGERO, et al, 2010;FOCK et al, 2012) e pode ser explicada por alterações nas concentrações plasmáticas de aminoácidos de cadeia ramificada (leucina, valina e isoleucina), os quais influenciam a regulação do centro da fome (FERRO-LUZZI e SPADONI, 1978).…”

Protein malnutrition effects of perivascular bone marrow microenvironment on the regulation of hematopoiesis

“…Está bem estabelecido na literatura que a DP/DPE compromete órgãos linfohematopoéticos -medula óssea (MO), baço e timo -com consequente modificação da resposta imune (KEUSCH, 2003a;FOCK, BLATT, et al, 2010;FOCK, ROGERO, et al, 2010;SCRIMSHAW, 2010;FOCK et al, 2012). Isto é evidenciado pela redução da migração celular, fagocitose, atividade bactericida e fungicida e alteração na produção de espécies reativas de oxigênio (CHANDRA, 1991;KEUSCH, 1994;NARDINELLI e BORELLI, 2001), nitrogênio e diminuição na síntese de fator de necrose tissular (TNF) -a e interleucinas (IL) -1a,…”

“…Como consequência da instalação da DP, os animais que receberam dieta hipoproteica apresentaram redução de peso corpóreo, devido ao aumento do catabolismo muscular observado na privação proteica, em que o organismo tende a utilizar aminoácidos provenientes da musculatura esquelética e, em menor proporção, da musculatura lisa (HUANG e FRAKER, 2003;ALVES et al, 2008;MALAFAIA et al, 2009 BORELLI et al, 2007;XAVIER et al, 2007;FOCK, ROGERO, et al, 2010;FOCK et al, 2012;. O número de plaquetas foi semelhante nos dois grupos avaliados e está de acordo com dados da literatura descritos desde 1978 (FRIED et al, 1978).…”