Antituberculosis Action of the Synthetic Peptide LKEKK

Objective: We previously synthesized the peptide LKEKK corresponding to sequences 16–20 of human thymosin-α₁ and 131–135 of human interferon-α₂ and showed that it was capable of exerting antimicrobial and anti-inflammatory effects in vitro and in vivo. In this study, the activity of the synthetic peptide LKEKK was investigated in a mouse model of tuberculosis induced by Mycobacterium bivis-bovinus 8. Methods: CBA mice were infected by injecting a suspension of M. bovis-bovinus 8 (0.1 mg in 0.2 mL of saline, ~100 bacterial bodies, subcutaneously). Beginning on day 7 after inoculation, two mice were sacrificed every two days, and the lungs were examined. Disease severity was assessed by visual inspection and calculated as the “lung injury index.” Results and Discussion: Therapy with peptide at doses of 0.01, 0.1, and 1 μg/kg (5 daily injections) significantly reduced the lung injury index of mice compared to animals in the control groups (no treatment and isoniazid treatment). Using [³H]LKEKK, it was shown that the high sensitivity of peritoneal macrophages and splenocytes of infected mice to the peptide was maintained for at least three weeks (K_d 18.6 and 16.7 nM for macrophage and splenocyte membranes, respectively). A study of cytokine production by splenocytes of infected mice showed that, on day 24 after treatment with the peptide (doses of 1 and 10 µg/kg), the secretion of IL-2 was restored to the level observed in uninfected animals. IFN-γ production by spleen cells of infected mice also significantly increased upon peptide treatment. At the same time, IL-4 production decreased in splenocytes. In addition, the peptide treatment stimulated the phagocytic activity of peritoneal macrophages, which was reduced due to tuberculosis infection. Conclusions: The synthetic peptide LKEKK increased the effectiveness of anti-tuberculosis therapy, as well as the strength of the immune response. The peptide can be used in complex therapy of tuberculosis.