(20.1, 84.0) 67.5 (26.2, 111.6) 11.6 (31.0, 215.3) 34.8 (6.6, 77.1) 52.0 (24.3, 94.8) 41.9 (28.2, 68.0) 15.0 (9.8, 21.0) 33.5 (10.1, 68.3) 85.5 (53.0, 164.0) 123.3 (85.0, 186.3) 22.0 (4.8, 51.1) SDP group (n = 10) 3.1 (1.8, 4.7) 48.8 (23.0, 99.8) 58.5 (29.0, 96.6) 44.5 (18.1, 78.9) 13.0 (4.1, 30.7) 30.0 (14.8, 58.6) 58.2 (16.6, 155.4) 17.0 (1.1, 45.5) 40.0 (19.0, 76.0) -7.2 (-14.5, -0.2) 24.5 (5.5, 56.3) 35.9 (8.6, 85.9) 47.0 (13.7, 101.0) 81.3 (52.3, 120.3) 14.0 (-2.5, 44.5) 25.0 (10.9, 52.6) 35.5 (11.5, 66.4) 66.2 (8.0, 166.1) 16.2 (0.7, 43.0) 42.5 (17.0, 81.0) 23.5 (11.1, 36.9) 16.7 (12.2, 21.5) 18.0 (5.3, 50.8) 73.5 (43.5, 135.4) 99.3 (69.9, 140.0) 5.7 (-1.0, 20.5) p value* 0.473 0.004 0.067 <0.001 <0.001 0.056 0.059 0.046 0.011 0.181 0.275 0.002 0.178 0.689 0.078 0.002 <0.001 0.052 0.011 0.166 <0.001 0.256 0.102 0.183 0.006 <0.Table

(20.1, 84.0) 67.5 (26.2, 111.6) 11.6 (31.0, 215.3) 34.8 (6.6, 77.1) 52.0 (24.3, 94.8) 41.9 (28.2, 68.0) 15.0 (9.8, 21.0) 33.5 (10.1, 68.3) 85.5 (53.0, 164.0) 123.3 (85.0, 186.3) 22.0 (4.8, 51.1) SDP group (n = 10) 3.1 (1.8, 4.7) 48.8 (23.0, 99.8) 58.5 (29.0, 96.6) 44.5 (18.1, 78.9) 13.0 (4.1, 30.7) 30.0 (14.8, 58.6) 58.2 (16.6, 155.4) MS023 side effects AZD3759 site 17.0 (1.1, 45.5) 40.0 (19.0, 76.0) -7.2 (-14.5, -0.2) 24.5 (5.5, 56.3) 35.9 (8.6, 85.9) 47.0 (13.7, 101.0) 81.3 (52.3, 120.3) 14.0 (-2.5, 44.5) 25.0 (10.9, 52.6) 35.5 (11.5, 66.4) 66.2 (8.0, 166.1) 16.2 (0.7, 43.0) 42.5 (17.0, 81.0) 23.5 (11.1, 36.9) 16.7 (12.2, 21.5) 18.0 (5.3, 50.8) 73.5 (43.5, 135.4) 99.3 (69.9, 140.0) 5.7 (-1.0, 20.5) p value* 0.473 0.004 0.067 <0.001 <0.001 0.056 0.059 0.046 0.011 0.181 0.275 0.002 0.178 0.689 0.078 0.002 <0.001 0.052 0.011 0.166 <0.001 0.256 0.102 0.183 0.006 <0.Table 2. Plasma cytokine concentrations of the HIV-infected participants [Median (IQR; pg/mL)]. * P-value < 0.001 was considered statistically significant after Bonferroni correction.HIV-infected individuals had significantly increased plasma GM-CSF, IFN-2, IL-12p70, IP-10 and VEGF, and much higher levels were observed in RDPs compared to SDPs (p < 0.001). Then we asked whether RDPs had higher levels of plasma cytokines than SDPs in chronic infection as in acute disease. As shown in Fig. 2, both RDPs and SDPs had high levels of plasma cytokines after viral set point, and had a second wave of cytokines storms during chronic stages. FGF-2, GM-CSF, IFN-, IL-13, IL-15, IL-1, IL-1ra and VEGF had increased more than 12-fold. 7 of 26 cytokines increased 7?2 fold, and 11 cytokines have less than 7-fold changes. Interesting, there is no significant difference on the levels and the time to reach peak value of the second wave between two groups (data not shown).Correlation among plasma cytokine concentrations during HIV-1 infection. HIV disease progression resulted in a significant modification of the interconnections between cytokines belonging to functionally distinct classes: the median correlation coefficients (0.890 vs. 0.524) were significantly different in SDPs and RDPs (p < 0.001), and they were both significantly different from plasma from HIV-uninfected (or healthy) subjects (0.186, p < 0.001) (Fig. 3). Furthermore, in RDPs, there were 146 (44.9 ) statistically significant correlations between the levels of individual cytokines. In contrast, in SDPs, there were 241 (74.2 ) such correlations (p < 0.001). Thus, the cytokine networks become more interlocked in SDPs than those in RDPs: 114 new correlations were established, and 19 correlations were lost. 97 pre-existing correlations increased in magnitude, 29 decreased, and 1 did not. For example, for IL-2, only correlations with IL-15, MCP-1, MIP-1 and TNF- were found in RDPs, while 11 new statistically significant correlations, including those with IL-4 and IL-10, were established for this cytokine in SDPs. In another example, a relatively weak correlation of IL-6 with IL-10 in RDPs (r = 0.647, p < 0.001) became a very strong one in SDPs (r = 0.993, p < 0.001).Some studies have previously shown that the cytokine cascade found in AHI might contribute to control of viral replication2,23. However, both the extent and duration of exponential cytokine expansion during acute infection are poorly understood2,22,24. Very few studies have been able to investigate the very early events during the first several weeks post infection, since the exact infection date is hard t.(20.1, 84.0) 67.5 (26.2, 111.6) 11.6 (31.0, 215.3) 34.8 (6.6, 77.1) 52.0 (24.3, 94.8) 41.9 (28.2, 68.0) 15.0 (9.8, 21.0) 33.5 (10.1, 68.3) 85.5 (53.0, 164.0) 123.3 (85.0, 186.3) 22.0 (4.8, 51.1) SDP group (n = 10) 3.1 (1.8, 4.7) 48.8 (23.0, 99.8) 58.5 (29.0, 96.6) 44.5 (18.1, 78.9) 13.0 (4.1, 30.7) 30.0 (14.8, 58.6) 58.2 (16.6, 155.4) 17.0 (1.1, 45.5) 40.0 (19.0, 76.0) -7.2 (-14.5, -0.2) 24.5 (5.5, 56.3) 35.9 (8.6, 85.9) 47.0 (13.7, 101.0) 81.3 (52.3, 120.3) 14.0 (-2.5, 44.5) 25.0 (10.9, 52.6) 35.5 (11.5, 66.4) 66.2 (8.0, 166.1) 16.2 (0.7, 43.0) 42.5 (17.0, 81.0) 23.5 (11.1, 36.9) 16.7 (12.2, 21.5) 18.0 (5.3, 50.8) 73.5 (43.5, 135.4) 99.3 (69.9, 140.0) 5.7 (-1.0, 20.5) p value* 0.473 0.004 0.067 <0.001 <0.001 0.056 0.059 0.046 0.011 0.181 0.275 0.002 0.178 0.689 0.078 0.002 <0.001 0.052 0.011 0.166 <0.001 0.256 0.102 0.183 0.006 <0.Table 2. Plasma cytokine concentrations of the HIV-infected participants [Median (IQR; pg/mL)]. * P-value < 0.001 was considered statistically significant after Bonferroni correction.HIV-infected individuals had significantly increased plasma GM-CSF, IFN-2, IL-12p70, IP-10 and VEGF, and much higher levels were observed in RDPs compared to SDPs (p < 0.001). Then we asked whether RDPs had higher levels of plasma cytokines than SDPs in chronic infection as in acute disease. As shown in Fig. 2, both RDPs and SDPs had high levels of plasma cytokines after viral set point, and had a second wave of cytokines storms during chronic stages. FGF-2, GM-CSF, IFN-, IL-13, IL-15, IL-1, IL-1ra and VEGF had increased more than 12-fold. 7 of 26 cytokines increased 7?2 fold, and 11 cytokines have less than 7-fold changes. Interesting, there is no significant difference on the levels and the time to reach peak value of the second wave between two groups (data not shown).Correlation among plasma cytokine concentrations during HIV-1 infection. HIV disease progression resulted in a significant modification of the interconnections between cytokines belonging to functionally distinct classes: the median correlation coefficients (0.890 vs. 0.524) were significantly different in SDPs and RDPs (p < 0.001), and they were both significantly different from plasma from HIV-uninfected (or healthy) subjects (0.186, p < 0.001) (Fig. 3). Furthermore, in RDPs, there were 146 (44.9 ) statistically significant correlations between the levels of individual cytokines. In contrast, in SDPs, there were 241 (74.2 ) such correlations (p < 0.001). Thus, the cytokine networks become more interlocked in SDPs than those in RDPs: 114 new correlations were established, and 19 correlations were lost. 97 pre-existing correlations increased in magnitude, 29 decreased, and 1 did not. For example, for IL-2, only correlations with IL-15, MCP-1, MIP-1 and TNF- were found in RDPs, while 11 new statistically significant correlations, including those with IL-4 and IL-10, were established for this cytokine in SDPs. In another example, a relatively weak correlation of IL-6 with IL-10 in RDPs (r = 0.647, p < 0.001) became a very strong one in SDPs (r = 0.993, p < 0.001).Some studies have previously shown that the cytokine cascade found in AHI might contribute to control of viral replication2,23. However, both the extent and duration of exponential cytokine expansion during acute infection are poorly understood2,22,24. Very few studies have been able to investigate the very early events during the first several weeks post infection, since the exact infection date is hard t.

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