Therapeutic Effect of Recombinant Mutated Interleukin 11 in the Mouse Model of Tuberculosis

• Published in: The Journal of infectious diseases 2016-08, Vol.214 (3), p.496-501
• Main Authors: Shepelkova, Galina, Evstifeev, Vladimir, Majorov, Konstantin, Bocharova, Irina, Apt, Alexander
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosols; Amino Acid Substitution; Animals; Disease Models, Animal; Escherichia coli; Female; Immunologic Factors - administration & dosage; Inflammation - pathology; Interleukin-11 - antagonists & inhibitors; Lung - pathology; Mice; Mutant Proteins - administration & dosage; Mycobacterium tuberculosis; PATHOGENESIS AND HOST RESPONSE; Recombinant Proteins - administration & dosage; Survival Analysis; Therapeutic Uses; Tuberculosis, Pulmonary - drug therapy
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiw176

Earlier we demonstrated that blocking of interleukin 11 (IL-11) by systemic administration of anti-IL-11 antibodies attenuates severity of Mycobacterium tuberculosis infection in mice. The substitution W147A in the IL-11 molecule creates the form of cytokine capable to disrupt gpl30/ILHR signaling complex formation, thus serving as a high-affinity specific antagonist of IL-11-mediated signaling. We hypothesized that this mutant form of IL-11 may serve as an effective tool for inhibition of native IL-11 activity in vivo.We established the recombinant W147A mutant form of IL-11 in an optimized Escherichia coli expression system and administered it as the aerosol in the lungs of M. tuberculosis-susceptible I/St mice infected with M.tuberculosis.Our results show that this therapeutic approach markedly inhibits tuberculous inflammation in lungs, increases the survival time of infected animals, and decreases expression of key inflammatory factors at the RNA and protein levels. These findings are a step toward clinical evaluation of the anti-IL-11 therapy for tuberculosis.