Table 2.

Virus titer (lg FFU/mL) after treatment of the influenza virus with KS-6469

Animal model/species	Experimental protocol	Result	Reference
Pulmonary aspergillosis C57BL/6 mice	Intraperitoneal administration of rIL-37 at doses of 1000, 100, 10 and 1 ng/mouse prior to infection	Decrease in the number of neutrophils in the BAL Suppression of NLRP inflammasome in the lungs Decreased IL-1β, IL-6, and IL-17A in the lung tissue Activation of IL-10 in the lung tissue Reduced signs of bronchial remodeling (collagenosis of lung tissue and metaplasia of bronchial epithelium) Suppression of lung infiltration with Th2/Th17 cells.	[48]
OVA-induced BA. C57BL/6 mice	Intranasal administration of rIL-37 at a dose of 1 μg/mouse 1 day prior to aerosol administration of OVA	Decreased eosinophil count in BAL and lung tissue Suppression of bronchial epithelium hyperplasia, mucus production and bronchial hyperreactivity Suppression of pro-inflammatory cytokines in BAL: IL-6, IL-12, IL-4, IL-5, and IL-13	[50]
HDM-induced AR BALB/c mice	Intranasal administration of rIL-37 at a dose of 1 μg/mouse in combination with nasal provocation with HDM	Threefold reduction in nasal hyperreactivity Decreased levels of allergen-specific antibodies of the IgE class Suppression of eosinophilic infiltration to the mucosa of the nasal cavity Suppression of the pro-inflammatory cytokines IL-4, IL-5, IL-13 and IL-17 in the nasal mucosa and activation of regulatory IL-10	[70]
OVA-induced BA BALB/c mice	Intranasal administration of rIL-37 at a dose of 1 μg/mouse in combination with allergen provocation	Decreased bronchial hyperreactivity and lung infiltration by pro-inflammatory cells (lymphocytes, neutrophils, and eosinophils) Inhibition of IL-4, IL-6, and IL-13 in lung tissue Decrease in proliferation and migration of respiratory smooth muscle cells and epithelial-mesenchymal transition	[68]
HDM-induced BA BALB/c mice	Intranasal administration of rIL-37 at a dose of 0.2 μg/mouse combined with sensitization or nasal provocation with HDM	Decrease in the number of eosinophils in BAL and lung tissue, decreased bronchial hyperreactivity IL-37 suppressed IL-4/13-induced production of CCL11 fibroblasts and respiratory smooth muscle cells	[69]

Note:

rIL-37 – recombinant interleukin-37;

BAL – bronchoalveolar lavage;

BA – bronchial asthma;

OVA – ovalbumin allergen;

HDM – house dust mite allergen.