Figure 5.
URMC-099 reduces Tat-induced inflammatory cytokine production in vivo. We stereotactically injected either 3 μl of sterile PBS or 3 μl of 3 μg/μl HIV-1 Tat1–72 700 μm deep into somatosensory cortex. We treated half of the mice receiving saline and half of the mice receiving Tat with twice a day peritoneal injections of 10 mg/kg URMC-099. The other mice were left untreated. After 24 h, we rapidly dissected and flash froze total brain tissue from around the injection site and prepared protein lysates for Luminex protein analysis. We measured the levels of TNF-α (A), MCP-1 (B), IL-6 (C), and IL-10 (D) present in 50 μg of total brain lysate for each animal. Tat exposure significantly increased levels of TNF-α, MCP-1, and IL-6 above saline control. URMC-099 treatment significantly decreased the production of these cytokines, and, in the case of TNFα and IL-6, reduced production to saline control levels. URMC-099 had no effect on the levels of cytokines in saline-treated animals. Tat exposure did not significantly induce production of IL-10, and URMC-099 treatment had no effect on IL-10 levels. Results are expressed as picograms of cytokine detected per milligrams of total brain protein lysate analyzed. *p < 0.05, **p < 0.01, ***p < 0.001. We analyzed data depicted in A–D by one-way ANOVA with Newman–Keuls post hoc test. Error bars indicate SEM. Sa, Saline; UR, URMC-099.