The LY294002 inhibitor levels of these cytokines and chemokines in the BC7/alginate group peaked at 24 h post infection and was sustained up to 5 days, although the levels of these chemokines and cytokines decreased by day 5. We observed similar delayed chemokine responses in CFTR knockout mice infected with BC7/alginate, but in these mice the chemokine levels were sustained up to 7 days post infection. KC/CXCL1 and MIP-2/CXCL2 are potent chemoattractants for phagocytes, and IL-1b and TNF-a, which stimulate the expression of KC/CXCL1 and MIP-2/CXCL2, play a critical role in recruitment of phagocytes to the site of infection and subsequent clearance of bacteria. Therefore, the delay in chemokine response as observed in the BC7/alginate group in normal mice may result in delayed phagocyte recruitment and attenuated bacterial clearance, and thus promote the establishment of bacterial infection. Consistent with our hypothesis, DBA2 mice, which is a susceptible mouse strain, are deficient in bacterial clearance due to an initial delay in phagocyte recruitment. Compared to sham-infected mice, animals infected with either BC7/PBS or BC7/alginate showed significant increases in MCP1, which recruits monocytes, and IL-17, a cytokine expressed by a subset of CD4 positive T cells. However, at all the time points examined, both MCP-1 and IL-17 were much higher in the BC7/ alginate group compared to the BC7/PBS group. In addition, while the levels of MCP-1 and IL-17 returned to almost baseline in the BC7/PBS group by 3 days, mice in the BC7/alginate showed significantly increased levels of these cytokines up to 5 days, compared to sham-infected animals. The level of IL-17 has been shown to be increased in CF airways and is implicated in the increased chemokine responses and development of tissue inflammation. Therefore, it is conceivable that sustained increased levels of IL-17 observed in the BC7/alginate group may contribute to increased chemokine response observed during the late phase of infection. We also observed increased levels of MIP-1b/CCL4 at 3 days post infection in the BC7/alginate group compared to the BC7/PBS group. Since MIP-1b also increases the production of IL-1b and TNF-a from leukocytes, it may also contribute to an increased chemokine and cytokine response during the later stage of infection in the BC7/alginate group. Together these results suggest that alginate may facilitate persistence of bacteria by delaying the initial chemokine and cytokine response that is required for recruitment of phagocytes. The increased levels of chemokines that is observed in the BC7/alginate group may be due to both the persistent bacterial load and also exaggerated chemokine response stimulated by the increase in IL-17 and MIP1b. Th1 response following bacterial infection has been shown to be beneficial to the host. CF patients.