There were dose-related increases in a variety of indicators of pulmonary inflammation, such as number of polymorphonuclear leucocytes, amounts of albumin and lactic dehydrogenase (LDH) in the bronchi and nitric oxide production of alveolar macrophages. Contradictory results were reported from an acute inhalation exposure

in guinea-pigs to non-soluble curdlan, schizophyllan and zymosan (300 µg/m3 for 40 min) [24]. There was no effect on the number of neutrophils in the airways, but a tendency to a decreased number of macrophages and lymphocytes. The discrepancy between the studies is related probably buy Sotrastaurin to the differences in dose levels, where P-glucan in low levels does not induce an inflammatory response. Another reason might be interspecies differences in lung macrophage function [25]. In the present in vitro experiments with PBMC, the dose level per cell was very high compared to environmental exposures. P-glucan caused a large increase in the secretion of IL-6, which was higher among subjects with sarcoidosis. This cytokine is a potent inducer of a general inflammatory response, involving several

cytokines such as IL-17 which GSK2118436 mouse has been related to granuloma formation. Secretion of the anti-inflammatory IL-10, as seen after the stimulation with P-glucan and LPS, will inhibit macrophages and the differentiation of Th2 cells into Th1 effector cells [26]. The secretion was higher among subjects with sarcoidosis, which is in agreement with previous studies where the secretion

of IL-10 from alveolar macrophages was higher among subjects with sarcoidosis compared to controls [27,28]. IL-10 has important anti-inflammatory properties and also supresses granuloma formation [29]. S-glucan was a moderate inducer of cytokines from PBMC. In previous experiments an intratracheal instillation of a soluble β-glucan from Niclosamide C. albicans (25–100 ug/animal) was found to induce neutrophil and eosinophil inflammation with increased local expression of a variety of inflammatory cytokines [IL-1β, IL-6, macrophage proteins and regulated upon activation normal T cell expressed and secreted (RANTES)][30]. This suggests that S-glucan and P-glucan trigger different mechanisms for cytokine secretion from PBMC. The relation between the P-glucan-induced release of all the cytokines measured and serum levels of IL-2R and IL-12 connects the PBMC reactivity with two major inflammatory markers of sarcoidosis [6]. The ability of PBMC to secrete IL-12 after stimulation with P-glucan also related to the duration of the disease, reflecting the increasing inflammatory changes developing in sarcoidosis and paralleling the relation between domestic exposure to NAHA and spontaneous secretion of IL-12.