6). Interestingly, high levels of IL-22 were also detected
in the BGJ398 concentration serum samples of individuals with latent (P = 0·002) and active TB infection (P = 0·003) compared to healthy controls (Fig. 6). IL-1β concentrations in serum of individuals with latent TB infection were increased significantly compared to healthy individuals (P = 0·02). The levels of IL-1β were also higher in individuals with active TB infection but were not statistically significant. Significantly elevated levels of IL-8 were detected in the serum of individuals with latent TB infection only. Mean IL-8 concentrations were significantly higher in latent TB group compared to healthy controls (P < 0·0001). However, the levels of IL-8 were higher but not statistically significant in individuals with active TB infection when compared to healthy individuals (Fig. 6); there was
no difference in the circulating levels of IL-17, IFN-γ (Fig. 6), IL-12p70, IL-2 and TNF-β (data not shown) in serum samples of healthy, latent and active TB subjects. The mean levels of IL-4 in serum of individuals with latent and active TB infection were significantly higher (P = 0·02) than the levels found in healthy subjects (Fig. 6). Levels of IL-5 and IL-10 cytokines were below the detection limit in both antigen-stimulated PBMC culture supernatants as well as in serum samples in all three groups of individuals (data not shown). The present study demonstrates small molecule library screening differential induction of IFN-γ-, IL-17- and IL-22-expressing CD4+ T cells in learn more circulation and following specific stimulation with mycobacterial antigens in TST-negative healthy controls, TST-positive latent and active TB subjects. While the expression of IFN-γ and other cytokines has been analysed in human plasma and PBMC supernatants ex vivo[32,33], the levels of IL-17- and IL-22-expressing CD4+ T cells
and granulocytes in the whole blood of TB patients is not well reported. Herein, we show that the percentage of individuals with active TB expressing IL-17-, IL-22- and IFN-γ-producing CD4+ T cells were decreased significantly compared to the individuals with latent TB infection and healthy controls (Fig. 1). However, such differences were not found in CD8+ T cells (data not shown). The reasons for the decreased IFN-γ-, IL-17- and IL-22-expressing CD4+ T cells in the circulation remain unclear. The differential expression of cytokines in circulation and in affected tissues such as lungs, spleen and lymph nodes have been described in tuberculosis [23,34]. It is possible that antigen-specific IFN-γ-, IL-17- and IL-22-producing CD4+ T cells are recruited to the affected tissues by chemokines released by infected resident macrophages and dendritic cells.