NIOSH 10/2006 adaptive immune responses in rats beta glucan fungal

March 1, 2008

: Inhal Toxicol. 2006 Oct;18(11):865-74. Links

Pulmonary exposure to 1 --> 3-beta-glucan alters adaptive immune

responses in rats.

• Young SH,

• JR,

• Antonini JM.

Health Effects Laboratory Division, National Institute for

Occupational Safety and Health, town, West Virginia 26505,

USA. sby5@...

1 --> 3-beta-glucans have been associated with increased pulmonary

inflammation in fungal-related indoor air problems. Epidemiological

studies have shown a correlation between increases in T-cell

proliferation and decreases in CD4+/CD8+ ratio after exposure to

fungi. The objective of the present investigation was to determine

the mechanisms by which 1 --> 3-beta-glucans affect immune responses

using an animal model. Rats received a single dose of zymosan A (2.5

mg/kg body weight) via intratracheal instillation (IT) and were

euthanized on days 1, 4, 6, 8, and 10 post IT. Bronchoalveolar

lavage was performed at each time point post-IT. Inflammation and

lung injury were assessed by measuring neutrophil infiltration into

bronchoalveolar lavage fluid (BALF) and by measuring albumin and

lactate dehydrogenase levels in BALF, respectively. Alveolar

macrophage activation was determined by chemiluminescence. Immune

response was characterized via immunophenotyping of bronchoalveolar

lavage cells and lymphocytes isolated from the lung-associated lymph

nodes. Upon challenge with zymosan, rats exhibited increased

inflammation and injury at early time points (days 1 and 4) post IT

exposure. Although elevations in neutrophil infiltration and

chemiluminescence had returned to control levels on day 4,

lymphocytes recovered from lung-associated lymph nodes continued to

proliferate and reached a maximum on day 6. The CD4+/CD8+ T cell

ratio from lymph nodes was lower in zymosan-treated rats than in

control rats. Zymosan treatment increased tumor necrosis factor

(TNF)-alpha, interleukin (IL)-6, IL-10, and IL-12p70 secretion in

BALF on day 1. In summary, rats exposed to zymosan had an increase

in acute inflammation, and the altered lymphocyte profiles were

consistent with the findings of epidemiology studies.

PMID: 16864404 [PubMed - indexed for MEDLINE]

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