Combination anti-inflammatory and antiviral therapy of influenza in a cotton rat model.
The cotton rat was evaluated as a model for anti-inflammatory and antiviral influenza therapy. Beginning 3 days after intranasal infection with 10(7) tissue culture infectious doses-50% (TCID)(50) of an H3N2 human influenza, animals were treated topically via intranasal lavage with a range of doses of triamcinolone acetonide (1, 4, or 16 mg/kg), alone or in combination with a neuraminidase inhibitor or anti-influenza convalescent serum. Pulmonary histopathologic changes were dramatically decreased in animals treated with 4 or 16 mg/kg of triamcinolone, with little additional benefit from addition of a neuraminidase inhibitor or topical serum, agents which were much less effective when used alone. A high degree of suppression of IFN-gamma levels was observed in all combinations where 4 or 16 mg/kg of triamcinolone were used. Viral replication was not prolonged by corticosteroid therapy. Tissue damage during influenza infection may be greatly reduced by combination antiviral and anti-inflammatory therapy.
Ottolini
Martin
M
Department of Pediatrics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA. mottolini@usuhs.mil
Blanco
Jorge
J
Porter
David
D
Peterson
Lisa
L
Curtis
Spencer
S
Prince
Gregory
G
D000081:Acetamides / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000627:therapeutic use*; D006146:Guanidines; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D053139:Oseltamivir; D011714:Pyrans; D051381:Rats; D012794:Sialic Acids / Q000627:therapeutic use*; D016205:Sigmodontinae; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000627:therapeutic use*; D053243:Zanamivir
D000081:Acetamides; D000998:Antiviral Agents; D005938:Glucocorticoids; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D053139:Oseltamivir; D009439:Neuraminidase; D014222:Triamcinolone Acetonide; D053243:Zanamivir