Table 1.

Impact of Interleukin-6 on viral pneumonitis and lung Injury.

Experimental model	Key findings	Reference
Infection of human epithelial cells with SARS-CoV	•SARS-CoV induces greater IL-6 when compared to Influenza-A virus and human parainfluenza virus type 2	[43]
Infection of monocytes/macrophages with SARS-spike protein	•Upregulation of IL-6	[60,61]
Murine SARS-CoV model	•Disease dependent on infiltrating monocytes, which produced high levels of IL-6, IL-1β and TNF	[62]
Influenza infection with IL-6 KO mice	IL-6 KO mice show •Increased mortality •Reduced macrophage phagocytic function •Fibroblast proliferation, migration and collagen deposition •Prevents viral induced neutrophil death	[63,64]
HSV-1 respiratory infection with IL-6KO mice	•IL-6 KO mice show increased mortality	[65]
Experimental ARDS induced by the intratracheal instillation of bacterial endotoxin	•Reduced pulmonary inflammation by the addition of recombinant IL-6	[66,67]
Infectious models of tuberculosis, pneumococcal pneumonia and pulmonary aspergillosis	•IL-6 KO mice show increased mortality in all infectious models	[[68], [69], [70]]
Bleomycin lung injury model with IL-6 neutralization	IL-6 neutralization resulted in: •Accelerated type 2 pneumocyte apoptosis •Neutrophilic inflammation •Accelerated lung fibrosis	[71]
Rat model of bacterial sepsis remote from the lung with tocilizumab	Tocilizumab (anti-IL-6) resulted in: •Reduced sepsis-induced pulmonary and renal inflammatory •Decreased mortality	[72]