Efficacy of Peptide T in the Rabbit Model of HSV-1-Induced Keratitis.
摘要
Peptide T is an octapeptide initially developed as an anti-HIV agent. Peptide T has been reported to inhibit some actions of tumor necrosis factor and to reduce the incidence and/or severity of herpes related lesions. In this study, Peptide T topical therapy was evaluated during epithelial herpetic keratitis in the rabbit ocular model. NZW rabbits were inoculated with 103 pfu McKrae strain HSV-1 by topical drop instillation. On day 3 PI, all rabbits were evaluated by slit lamp biomicroscopy and ocular disease was graded on an increasing scale of severity. Animals were divided into groups with matched ocular disease, and topical therapy, 9x/day for 5 days was initiated as follows: Peptide T (10μg, 1μg, 100ng, 10ng, 1ng, 100pg, 10pg and 1 pg/ml), TFT, or Placebo Peptide 10 μg and 100ng/ml. TFT, was highly effective in reducing the development of HSV-1 ocular disease. Placebo Peptide therapy was not effective in slowing progression of HSV-1-induced disease. Topical Peptide T therapy demonstrated a biphasic response with enhanced anti-herpetic activity most evident in the physiological range (e.g. at 100 and 10ng/ml concentrations). At the higher Peptide T concentrations (μg/ml) the efficacy was blunted and the compound may have demonstrated a slight toxicity to the epithelial surface (epithelial cell sloughing). At the 10 and 1 pg/ml concentrations, Peptide T was ineffective in slowing HSV ocular disease progression. Clinical disease in the 100 and 10ng/ml Peptide T therapy groups was identical to TFT therapy. HSV recovery was reduced in the Peptide T and in TFT-treated eyes. Placebo peptide did not alter virus recovery. In the current study, Peptide T activity was 1,000 to 10,000 times more active than TFT (0.1%formulation). The development of a class of antiviral agents that are active in the ng/ml range will alleviate potential toxicity and drug resistance, problems currently encountered with nucleoside analog antiviral therapies.