Local pulmonary immune stimulation by the Toll-like receptor 2 and 6 ligand MALP-2 in rats is age dependent

Recent studies indicate that the pulmonary immune response in humans and experimental animals is different in newborn, adult and elderly age groups. The aim of this study was to investigate the influence of age on the leukocyte composition in different lung compartments and peripheral blood of weaned and adult rats. A mycoplasma-like inflammatory response was mimicked by intratracheal application of the synthetic macrophage-activating lipopeptide-2 (MALP-2) which activates macrophages and other cells via the Toll-like receptor (TLR) 2 and 6. TLR 2 and 6 mRNA expressions were investigated by semiquantitative RT-PCR in cells of the bronchoalveolar lavage (BAL) and lung interstitium. Weaned Lewis rats (3-4 weeks old) and adults (12-14 months old) were treated with vehicle control or MALP-2. Cytokines and cell infiltration were measured in the BAL and lung interstitium. In control rats, no differences in TLR 2 and 6 mRNA expression level were found between the age groups. After MALP-2 treatment, the maximum of MCP-1 concentration in the BAL fluid was reached in weaned rats after 4 h and in adults after 2 h. The TNF-alpha maximum was measured after 2 h in both age groups. Three days after MALP-2 the numbers of different leukocyte subsets were significantly increased in the BAL of both groups. In contrast, in the lung interstitium MALP-2 induced a leukocyte increase in adult rats but not in weaned rats. In conclusion, data on pulmonary immune responses from one a e group and one lung compartment should not be generalized or extrapolated to other groups. (c) 2007 Elsevier B.V. All riahts reserved.